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UNITED  STATES  MARINE  HOSPITAL  SEllVIOE. 


REPORT 


ON  THE 


ETIOLOGY  AND  PREVENTION 


OP 


YELLOW  FEYEE. 


BY 


GEORGE   M.   STERNBERG, 

LIEUT.   COLOiSrHiXj   J^NJD   SXJ-RGJ-JilOjSr,  XJ.  S.  ^VKINIY. 


Published  by  order  of  the  Secretary  of  the  Treasury,  iu  accordance 
■with  the  act  of  Congress  apjiroved  March  3,  1887. 


WASHINGTON: 

GOVERNMENT  PRINTING  OFFICE. 
1S90. 


Tkeasury  Dkpartment, 

Document  Js'o.  1328. 
Marine- Hospital  Service. 


LETTER  OF  THE  SUPERVISING  SURGEON-GENERAL 


Treasury  Department, 
Office  of  the  Supervising  Surgeon-General, 

U.  S.  Marine  Hospital  Service, 

July  11,  1890. 
Sir:  Referring   to  the   accompanying  report  of    Maj.  George  M. 
Sternberg,  surgeon  U.  S.  Army,  of   his  researches   relating  to   the 
etiology  of  yellow  fever,  I  have  the  honor  to  recommend  that  it  be 
immediately  printed  as  a  special  report  from  this  Bureau. 
Very  respectfully,  your  obedient  servant, 

John  B.  Hamilton, 
"  Supervising  Surg  eon- General  Marine  Hospital  Service. 

Hon.  William  Windom, 


Secretary  of  the  Treasury. 
Approved,  July  11,  1890. 


William  Windom, 

Secretary  of  the  Treasury. 


EESEAECHES 


RELATING   TO   THE 


ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER, 

MADE   BY 

GEORGE    M.    STERXBEEG,    M.    D., 

Lieut.  Colonel  and  Suegeon,  U.  S.  Army, 

By  direction  of  the  President,  in  pnrsnance  of  an  act  of  Congress  approved  March  3, 
1887,  "making  appropriations  for  sundry  civil  expenses  of  the  Government." 


Submitted  June  21,  1890, 


ORDERS. 


Special  Orders  ?  Headquarters  of  the  Army, 

No.  93.        }  Adjutant-General's  Office, 

Washington,  Ajml  '23,  1888. 

[Extract] 

1.  The  following  order,  received  from  the  War  Department,  is  substituted  for  para- 
graph 13,  Special  Orders  No.  89,  April  18,  1888,  from  this  ofSce,  which  is,  by  direction 
of  the  Secretary  of  War,  revoked  : 


War  Department,  Washington,  Ajml  21, 
By  direction  of  the  President,  in  pursuance  of  the  authority  contained  in  the  pro- 
visions of  the  act  of  Congress,  approved  March  3,  1887,  "making  appropriations  for 
sundry  civil  expenses  of  the  Government,"  etc.,  relating  to  the  methods  of  prevent- 
ing the  spread  of  epidemic  diseases,  Maj.  George  M.  Sternberg,  Surgeon  U.  S.  Army, 
will  proceed  to  the  Island  of  Cuba  for  the  purpose  named  in  the  letter  of  the  Presi- 
dent addressed  to  the  Secretary  of  War  on  the  17th  instant,  and  upon  the  completion 
of  this  duty  will  return  to  his  proper  station  and  submit  his  report  to  the  President 
on  or  before  June  2.5,  1888. 
The  travel  enjoined  is  necessary  for  the  public  service. 

Wm.  C.  Endicott, 


By  command  of  Lieutenant-General  Sheridan : 


Secretary  of  War. 


E.  C.  Drum, 
Adjutant-  General. 


Special  Orders,    ?  Headquarters  of  the  Armt, 

No.  224.         i  Adjutant- General's  Office, 

Washington,  September  26,  1888. 

[Extract.] 


8.  The  following  order  has  been  received  from  the  War  Department: 

Wak  Department,  Washington,  September  26,  1888. 
By  direction  of  the  President,  Maj.  George  M.  Sternberg,  Surgeon  U.  S.  Army,  will 
proceed  to  Decatur,  Ala.,  and  to  such  other  points  in  the  infected  districts  of  the 
Southern  St;itos  as  he  may  deem  necessary  to  continue  his  scientific  investigations  of 
yellow  fev«r. 

E.  Macfeely, 
Acting  Secretary  of  War. 

7 


8  ORDERS. 

Upon  the  completion  of  the  duty  assigned  him  in  this  order,  Major  Sternberg  will 
return  to  his  proper  station. 
The  travel  enjoined  is  necessary  for  the  public  service. 


By  command  of  Major-General  Schofield: 


R.  C.  Drum, 
Adjutan  t-  Gen  cral. 


Special  Orders,  ?'  Headquarters  of  the  Army, 

No.  30.         S  Adjuta^tt  General's  Office, 

Washington,  February  5,  1889. 

[Extract.! 


16.  The  following  order  has  been  received  from  the  War  Department : 

War  DEPARTMEN'r,  Washington,  February  4,  1889. 
By  direction  of  the  President,  in  pursuance  of  the  authority  contained  in  the  pro- 
visions of  the  act  of  Congress,  approved  March  3,  18S7,  "making  appropriations  for 
sundry  civil  expenses  of  the  Government,"  etc.,  relating  to  the  methods  of  prevent- 
ing the  spread  of  epidemic  diseases,  Maj.  George  M.  Sternberg,  Surgeon  U.  S.  Army, 
will  proceed  to  the  Island  of  Cuba  for  the  purpose  named  in  the  letter  of  the  Presi- 
dent addressed  to  the  Secretary  of  War  April  17,  1888,  and  upon  the  completion  of 
this  duty  will  return  to  his  proper  station  and  submit  his  report  to  the  President. 
The  travel  enjoined  is  necessary  for  the  i)ublic  service. 

Wm.  C.  Exdicott, 

Secretary  of  War. 


By  command  of  Major-General  Schofield. 

R.  C.  Drum, 
Adjutant-General. 


ACKNOWLEDGMENTS. 


I  am  indebted  to  tlie  president  and  trustees  of  the  Johns  Hopkins 
University,  of  Baltimore,  for  ttie  title  and  privileges  of  Fellow  by 
Courtesy  in  the  University,  and  to  Dr.  jS".  H.  Martin,  professor  of  biology, 
and  Dr.  Wm.  H.  Welch,  professor  of  pathology,  for  laboratory  facili- 
ties and  valuable  assistance  in  various  ways. 

In  Havana,  through  the  courtesy  of  the  governor-general  of  the 
island;  of  Dr.  Antonio  Pardinas,  medical  inspector-general ;  and  of  Dr. 
Fernandes  Malo,  director  of  the  military  hospital,  I  have  had  free 
access  to  the  wards  of  this  hospital,  and  have  been  able  to  make  nu- 
merous autopsies  in  typical  cases  of  yellow  fever.  I  desire  to  express 
my  obligations  to  these  gentlemen  and  to  the  medical  officers  of  the 
Spanish  army  on  duty  at  this  hospital.  Also  to  Dr.  Emiliano  Nunez, 
director  of  the  new  and  admirable  civil  hospital,  Nuestra  Senora  de  las 
Mercedes. 

Also  to  Dr.  Santos  Fernandos,  and  the  gentlemen  connected  with 
the  bacteriological  laboratory  of  the  "  Cronica  Medica-Quirurgica,"  for 
valuable  assistance  in  the  preparation  of  culture  material,  etc. ;  to  Dr. 
Daniel  M.  Burgess,  United  States  sanitary  inspector.  Marine  Hospital 
Service,  at  Havana,  for  assistance  at  autopsies,  and  in  many  other  ways 
during  my  entire  stay  in  Cuba ;  to  Dr.  Carlos  Finlay,  and  his  associate  in 
bacteriological  work,  Dr.  Claudio  Delgado;  to  Dr.  Francis  I.  Vildosola 
for  the  use  of  his  laboratory,  in  which  my  culture  material  was  pre- 
pared during  the  summer  of  1889,  by  Dr.  Emilio  Martinez.  The  last- 
named  gentleman  has  rendered  most  valuable  services  as  my  assistant 
during  the  past  year  both  in  Cuba  and  in  Baltimore.  During  my  stay 
at  Decatur,  Ala.,  in  1888,  I  received  valuable  assistance  from  Dr. 
Jerome  Cochran,  health  officer  of  the  State  of  Alabama,  and  from  Dr. 
B.  F.  Cross,  Dr.  E.  J.  Conyngton,  and  Dr.  E.  M.  Littlejohn,  practicing 
physicians  in  Decatur. 

Some  of  my  photomicrographs  have  been  made  at  the  Hoagland 
Laboratory,  Brooklyn,  with  the  kind  assistance  of  Dr.  C.  N.  Hoagland. 
Dr.  James  E.  Eeeves,  of  Chattanooga,  Tenu.,  has  kindly  prepared  for 
me  a  series  of  sections  from  twenty-five  of  my  cases,  which  I  have 
placed  beside  my  own  and  those  of  my  laboratory  assistant,  Dr.  Mar- 

9 


10  ACKNOWLEDGMENTS. 

tinez,  in  the  series  submitted  with  this  report.  Dr.  VTilliam  T.  Couucil- 
man,  associate  in  pathology  in  the  Johns  Hopkins  University,  has  at 
my  request  examined  and  reported  upon  this  entire  series  of  slides. 

Dr.  F.  P.  Mall,  formerly  associate  in  pathology  iu  the  Johns  Hopkins 
TTniversity,  has  also  examined  for  me  some  pathological  material  and  a 
series  of  slides.  My  thanks  are  due  to  the  Supervising  Surgeon-General 
of  the  Marine  Hospital  Service  for  promptly  filling  my  requisitions  aud 
approving  my  accounts. 


INTRODUCTION. 


The  present  report  embodies  an  account  of  the  researches  made  by 
the  writer  in  compliance  with  the  foregoing  orders. 

My  investigations  in  Brazil  and  Mexico,  made  in  1887,  were  in  com- 
pliance with  orders  received  about  the  1st  of  May,  1887,  in  which  I  am 
especially  instructed  to  complete  my  investigations  by  the  1st  of 
October  of  the  same  year.     Thp.  following  is  a  copy  of  this  order: 

Washixgtox,  Ajn-il  29,  18S7. 

Sir  :  Referring  to  the  act  providing  for  snndry  civil  expenses  of  the  Governmr-nt 
for  the  year  ending  June  30,  1858,  especially  to  the  clause  providing  for  the  investi- 
gation of  yellow  fever  by  inoculation,  as  follows :  "And  the  President  is  further 
authorized  to  use  of  the  same  unf-xpended  bahance  a  sum  not  exceeding  §10,000  for 
the  purpose  of  investigating  the  merits  of  the  method  practiced  in  Mexico  and 
Brazil  for  preventing  yellow  fever  by  inoculation,"  you  are  hereby  directed,  under 
authority  of  said  act,  to  proceed  to  liio  de  Janeiro,  where  you  will  collate  the  docu- 
mentary and  other  evidence  of  the  experiments  by  Dr.  Freire.  Having  thoroughly 
familiarized  yourself  with  the  claims  of  Dr.  Freire,  yon  will  proceed  in  person  to 
inquire  at  the  Jnra-Juba  Hospital  and  such  other  jilaces  as  may  occur  to  you  after 
your  arrival  at  Rio  : 

First.  The  source  from  which  the  culture  supply  is  secured,  which  will  involve — 

(a)  The  examination  of  the  alleged  germ  as  shown  yon  by  those  engaged  in  the 
business  of  inoculation. 

(&)  Verification  of  the  cultivation  and  process  of  attenuation  adopted. 

Second.  The  method  of  the  inoculation,  which  you  will  see  verified,  if  practicable, 
on  actual  cases. 

Third.  Ton  will  report  your  opinion  on  the  results  attained  by  the  process  after  a 
careful  examination  of  the  cases  which  have  previously  been  subjected  to  inocula- 
tion. In  forming  your  judgment  of  these  results  you  will  tate  into  consideration  the 
following  points : 

(a)  Personal  characteristics  of  the  patient ;  age,  race,  nativity,  sex,  previous  sus- 
ceptibility. 

(6)  The  period  since  last  inoculation;  number   of  times  exposed  to  the  contagion. 

Having  completed  this  study,  you  will  then  proceed  to  Mexico  by  the  shortest  and 
most  practicable  route  and  investigate,  in  the  same  manner,  the  method  of  inocula- 
tion practiced  by  Dr.  Carmona  y  Valle,  and  the  same  method  will  be  observed  in 
conducting  the  inv^estigation. 

While  your  attention  is  directed  specifically  to  these  points  and  details,  with  the 
expectation  that  they  will  be  carefully  kept  in  view  and  adopted  for  your  guidance, 
they  are  not  intended  to  exclude  such  additional  methods  and  means  of  investiga- 
tion as  your  judgment  may  approve  in  the  thorough  and  careful  accomplishment  of 
the  purposes  of  your  mission. 

In  order  that  every  facility  may  be  afforded  you  for  the  prosecution  of  the  work, 
you  will  make  known  your  errand  to  the  United   States  minister  at  Rio  de  .Janeiro 

11 


12  INTRODUCTION. 

and  the  United  States  minister  at  the  City  of  Mexico,  respectively,  and  request  them 
to  use  their  influence  in  procuring  such  access  to  the  hosjiitals  and  such  other  sources 
of  information  as  you  may  desire.  You  will  refrain  from  making  j)uhlication  of  your 
investigations  and  the  conclusions  reached  by  yon  until  you  shall  have  submitted  to 
me  the  completed  report.  You  will  forward  your  vouchers  for  traveling  expenses, 
from  time  to  time,  to  the  Supervising  Surgeon-General  of  the  Marine-Hospital  Serv- 
ice for  payment,  certifying  the  same  before  any  consular  officer  where  you  may  be 
at  the  time. 

You  will  also  make  requisitions  on  the  Supervising  Surgeon-General  for  such  scien- 
tific appliances  as  may  be  necessary  to  accomplish  the  object  of  your  journey. 

It  is  expected  that  your  investigation  will  be  completed  by  the  1st  of  October. 

Grover  Cleveland. 

Maj.  George  M.  Sternberg, 

Surgeon,  U.  S.  Army. 

In  compliauce  with  these  orders  I  submitted  a  report  to  the  President 
in  March,  1888,  which  is  published  in  the  annual  volume  of  the  Marine- 
Hospital  Service  for  1889. 

In  transmitting  this  report  I  say: 

I  have  the  honor  to  transmit  herewith  a  detailed  report  of  the  investigations  which 
I  have  made  in  compliance  with  your  instructions  dated  April  29,  1887. 

The  conclusions  reached  (MS.,  pp.  280  to  283)  are  definite  so  far  as  the  methods  of 
inoculation  practiced  in  Brazil  and  in  Mexico  are  concerned,  but  xiufortunately  the 
question  of  the  etiology  of  yellow  fever  is  left  in  an  unsettled  state.  The  limit  as  to 
time  fixed  by  my  orders,  and  the  fact  that  the  disease  was  not  prevalent  either  in 
Brazil  or  in  Mexico  at  the  time  of  my  visits  to  those  countries,  have  made  it  impossible 
for  me  to  make  certain  researches  which  I  consider  extremely  important  in  connec- 
tion with  the  subject  under  investigation. 

The  orders  given  me  in  April,  18S8,  were  intended  to  afford  me  the 
opportunity'  I  desired  for  continuing  my  investigations  during  the  epi- 
demic season  at  one  of  the  permanent  centers  of  infection,  but  the  time 
was  again  limited  through  a  misapprehension  with  reference  to  the 
availability  of  the  appropriation  after  the  end  of  the  fiscal  year,  and  I 
was  required  to  return  to  my  proper  station  and  submit  my  report  to 
the  President  "  on  or  before  June  25, 1888." 

The  report  submitted  in  compliance  with  this  requirement  was  a  brief 
one.  At  my  request  it  was  subsequently  returned  to  me  and  is  embod- 
ied in  the  present  report.  In  the  autumn  of  1888,  yellow  fever  having 
appeared  in  epidemic  form  in  Florida  and  Alabama,  I  requested  author- 
ity to  proceed  to  the  infected  district  for  the  purpose  of  continuing  my 
investigations,  and  received  the  orders  dated  September  26, 1888. 

I  selected  Decatur  as  the  locality  for  my  researches,  rather  than  Jack- 
sonville, because  the  comparatively  small  mortality  in  the  last-named 
city  led  some  physicians  to  question  the  diagnosis,  and  because  my 
friend.  Dr.  Jerome  Cochran,  State  health  ofBcer,  was  at  Decatur,  and 
I  was  confident  that  he  would  do  all  that  was  in  his  power  to  aid  me  in 
my  scientific  researches,  an  expectation  which  was  fully  realized. 

Not  having  arrived  at  any  definite  conclusion  as  to  the  sjyecijic  cause 
of  the  disease  under  investigation,  I  again  asked  to  be  sent  to  Cuba 
during  the  epidemic  season  of  1889,  and  received  the  orders  dated  Feb- 


INTRODUCTION.  13 

ruary  5,  1889,  which  did  not  restrict  me  as  to  time  and  enabled  me  to 
spend  the  entire  summer  in  Havana. 

The  material  obtained  from  thirty  autopsies  made  in  Havana  during 
the  past  summer  and  the  study  of  the  various  microorganisms  isolated 
in  my  culture  experiments  have  fully  occupied  my  time  since  my  return 
from  Cuba. 

I  have  now  commenced  writing  a  report  because  I  feel  that  an  ac- 
count of  what  I  have  been  doing  during  the  past  two  years  is  due,  and 
not  because  I  have  brought  my  investigation  to  a  successful  termina- 
tion, or  because  I  feel  that  there  is  nothing  more  to  be  done. 

Ko  one  can  regret  more  than  I  do  that  the  question  of  the  etiology  of 
yellow  fever  is  not  yet  solved  in  a  definite  manner,  but  I  at  least  have 
not  to  reproach  myself  with  want  of  diligence  or  failure  to  embrace 
every  opportunity  for  pursuing  the  research.  The  difficulties  have 
proved  to  be  much  greater  than  I  anticipated  at  the  outset.  If  the  task 
before  me  had  been  to  find  an  organism  in  the  blood,  like  that  of  relaps- 
ing fever  or  of  anthrax,  or  an  organism  in  the  organs  principally  in- 
volved, as  in  typhoid  fever,  or  leprosy,  or  glanders,  or  in  the  intestine, 
as  in  cholera,  the  researches  I  have  made  could  scarcely  have  failed  to 
be  crowned  with  complete  success.  But  this  has  not  proved  to  be  the 
case,  and  among  the  microorganisms  encountered  there  is  not  one 
which  by  its  constant  presence  and  special  pathogenic  power  can  be 
shown  indisputably  to  be  the  specific  infectious  agent  in  this  disease. 

If  I  have  not  succeeded  in  making  a  positive  demonstration  which 
will  satisfy  the  exactions  of  science  I  have  at  least  been  able  to  exclude 
in  a  definite  manner  a  majority  of  the  microorganisms  which  I  have 
encountered  in  my  culture  experiments,  as  well  as  those  which  various 
other  investigators  (Freire,  Carmona,  Finlay,  Gibier)  have  supposed  to 
be  the  specific  cause  of  the  disease.  I  shall  endeavor  to  give  an  exact 
account  of  the  characters  of  these  various  microorganisms  and  of  the 
evidence  upon  which  I  feel  justified  in  excluding  them  from  considera- 
tion from  an  etiological  point  of  view. 

While  this  is  much  less  than  I  had  aimed  at  and  hoped  for,  I  trust 
that  it  will  be  considered  amj)le  compensation  for  the  time  and  money 
expended,  and  I  am  sure  that  the  information  obtained  can  not  fail  to 
be  of  value  in  guiding  future  investigators  in  this  field  of  research. 

I  desire  here  to  quote  the  following  i)aragraphs  from  a  paper  read  at 
the  quarantine  conference  held  in  Montgomery,  Ala.,  in  March,  1889, 
just  before  my  last  visit  to  Havana: 

I  may  say  before  going  any  further  that  my  faith  in  a  living  infections  agent  as 
the  specific  cause  of  this  disease  is  by  no  means  diminished  by  my  failure  thus  far  to 
demonstrate  the  exact  form  and  nature  of  this  hypothetical  "germ."  The  present 
state  of  knowledge  with  reference  to  the  etiology  of  infectious  diseases  in  general 
and  well  known  facts  relating  to  the  origin  and  spread  of  yellow-fever  epidemics 
fully  justify  such  a  belief.  The  a  priori  grounds  for  such  faith  I  stated  as  long  ago 
as  1873  in  a  paper  published  in  the  American  Journal  of  the  Medical  Sciences  (July, 
1873) ;  and  the  jirogress  of  knowledge  since  that  date  has  all  been  in  the  direction  of 


14  INTRODUCTION. 

supporting  this  a  priori  reasouiug.  But  yellow  fever  is  by  no  means  the  only  infec- 
tious disease  in  which  satisfactory  evidence  of  the  existence  of  a  living  infectious 
agent  is  still  wanting.  In  the  eruptive  fevers  generally  no  demonstration  has  been 
made  of  the  specific  etiological  agent — at  least  none  which  has  been  accepted  by 
competent  pathologists  and  bacteriologists.  Again,  in  the  infectious  disease  of  cattle 
known  as  pleuropneumonia,  notwithstanding  very  extended  researches  by  compe- 
tent investigators  in  various  parts  of  the  world,  no  satisfactory  demonstration  of  the 
germ  has  been  made.  The  same  is  true  of  hydrophobia,  in  which  disease  we  are  able 
to  say  with  confidence  the  infectious  agent  is  present  in  the  brain  and  spinal  cord  of 
animals  which  succumb  to  rabies  ;  this  infectious  agent  is  destroyed  by  a  tempera- 
ture which  is  fatal  to  known  pathogenic  microorganisms  (65'^  C),  and  by  varions 
germicide  agents,  yet  all  efforts  to  cultivate  it  or  to  demonstrate  its  presence  in  the 
infectious  material  by  staining  processes  and  microscopical  examination  have  thus 
far  been  unsuccessful. 

You  are  aware  that  my  first  effort  to  solve  the  etiology  of  yellow  fever  was  made 
10  years  ago.  As  a  member  of  the  Havana  yellow-fever  commission  of  the  National 
Board  of  Health  I  had  an  opportunity  to  make  researches  which,  in  advance  of  the 
effort,  I  fondly  hoped  might  lead  to  a  demonstration  alike  creditable  to  American 
science  and  useful  as  a  basis  for  preventive  and  curative  measures  in  this  pestilential 
malady,  which  has  destroyed  the  lives  of  so  many  of  our  fellow-citizens,  and  has  so 
largely  interfered  with  the  material  progress  of  certain  sections  of  the  United  States. 
I  knew  from  personal  experience  the  malignant  nature  of  the  disease,  and  the  futil- 
ity of  the  various  modes  of  treatment  which  had  been  resorted  to  in  the  effort  to  com- 
bat it.  It  was  therefore  with  the  deepest  interest  as  well  as  with  strong  hopes  of 
success  that  I  went  to  an  endemic  focus  of  the  disease  to  search  for  the  yellow  fever 
germ.  The  recent  (1873)  demonstration  of  the  spirillum  of  relapsing  fever  in  the 
blood  of  patients  suffering  from  this  disease,  and  the  recognized  facts  relating  to  the 
etiology  of  anthrax,  considered  in  connection  with  the  current  notions  relating  to 
the  pathology  of  yellow  fever,  led  me  to  hope  that  the  discovery  would  be  an  easy 
one.  I  was  familiar  with  the  most  approved  metho  Is  of  mounting  and  staining  micro- 
organisms, and  was  provided  with  the  best  high-power  objectives  that  could  be  pro- 
cured, tne  one-twelfth  and  one-eighteenth  inch  homogeneous  oil-immersion  object- 
ives of  Karl  Zeiss,  of  Jena,  Germany.  Not  only  did  I  feel  that  I  was  equipped  for  the 
recognition  of  any  microorganism  which  might  prove  to  be  present  in  the  blood,  but 
I  was  prepared  to  photograph  it,  and  thus  to  show  to  others  what  I  might  see  in  blood 
drawn  from  the  circulation  of  yellow-fever  patients.  You  know  the  result  of  this  in- 
vestigation; ninety-eight  specimens  from  forty -one  undoubted  cases  of  yellow  fever 
were  carefully  studied,  and  one  hundred  and  five  photographic  negatives  were  made, 
which  showed  satisfactorily  everything  demonstrable  by  the  microscope.  But 'no 
microorganism  was  discovered.  I  shall  presently  show  you  upon  the  screen  a  photo- 
micrograph of  yellow-fever  blood,  made  in  Havana  at  the  time  mentioned,  so  that  you 
may  judge  of  the  performance  of  my  Zeiss  one-eighteenth  inch  objective,  and  have 
ocular  evidence  that  no  microorganism  demonstrable  by  this  magnificent  lens  was 
present  in  it.  I  may  say  here  that  my  culture  experiments  made  in  Havana  last 
spring,  in  which  blood  taken  from  one  of  the  cavities  of  the  heart  as  soon  as  possible 
after  death  was  introduced  into  various  nutritive  media,  gave  alike  negative  result. 

Out  of  ten  cases  in  which  I  made  the  autopsy,  in  the  military  hospital  at  Havana, 
a  development  of  microorganisms  occurred  in  two  only.  In  the  exceptional  cases  I 
obtained  a  bacillus  which  subsequent  researches  showed  to  be  identical  with  a  bacil- 
lus constantly  found  in  the  alimentary  canal  of  healthy  persons — bacterium  coli  com- 
mune of  Escherich. 

The  absence  of  microorganisms  from  blood  drawn  from  the  finger  during  life  or 
from  the  heart  after  death  can  not,  however,  be  accepted  as  evidence  that  there  are 
no  parasitic  organisms  anywhere  in  the  tissues.  The  bacillus  of  typhoid  fever,  for 
example,  is  rarely  found  in  the  circulating  fluid,  although  it  must  be  transported  in 


_     INTKODUCTION.  15 

the  blood  curreot  to  the  various  organs  iu  which  foci  of  growth  are  found  which 
contain  numerous  Lactlli.  Such  foci  are  especially  abundant  in  the  spleen,  but  even 
in  this  organ  many  thin  sections  may  be  made  before  a  single  focus  of  development 
is  encountered. 

Having  failed  to  find  the  yellow  fever  germ  in  the  blood,  we  may  still  admit  that, 
as  in  typhoid,  it  is  perhaps  only  to  be  found  in  the  organs  principally  involved  in  the 
morbid  process.  This  reasoning  has  led  me  to  give  special  attention  to  an  examina- 
tion of  the  liver  and  kidney,  both  by  the  culture  method  and  by  the  examination  of 
thin  sections.  Both  methods  have  given  me  positive  results  so  far  as  the  occasional 
presence  of  microorganisms  is  concerned,  but  both  are  in  accord  in  failing  to  demon- 
strate the  constant  presence  of  any  particular  organism.  In  my  culture  experiments 
made  in  Havana  last  year  the  microorganism  most  frequently  encountered  was  my 
bacillus  a,  already  referred  to  as  found  in  two  out  often  cases  in  cultures  from  blood 
drawn  from  the  heart.  Naturally  I  have  given  much  attention  to  this  bacillus,  and 
it  was  only  after  an  extended  series  of  comparative  experiments  that  I  gave  up  the 
hope  that  it  might  be  concerned  in  the  etiology  of  the  disease  under  consideration. 

These  comparative  experiments  forced  me  to  the  conclusion  that  this  is  the  same 
bacillus  as  was  found  by  Emmerich  in  cholera  cadavers  at  Naples,  and  that  it  cor- 
responds with  the  bacterium  coli  commune  of  Escherich. 

In  my  researches  by  the  method  of  staining  thin  sections  of  the  tissues  hardened  in 
alcohol  I  have  encountered  several  different  microorganisms,  but  no  one  of  these 
has  been  found  in  a  series  of  cases.  One,  the  bacillus  of  Lacerda  and  Babes,  I  have 
found  only  iu  material  brought  from  Dr.  Lacerda's  laboratory  in  Brazil,  and  in  two 
only  out  of  nine  cases  represented  by  material  from  this  source.  In  one  of  my 
Havana  cases,  in  which  the  material  was  collected  by  my  friend,  Dr.  Burgess,  in 
1887,  a  long  bacillus  was  found  in  the  kidney,  for  the  most  part  in  the  glomeruli.  la 
a  case  in  which  I  made  the  autox^sy  in  Havana  last  sirring  a  micrococcus,  grouped  in 
fours,  was  found  in  the  kidney. 

Evidently,,  if  any  one  of  these  microorganisms  was  found  in  a  considerable  series 
of  cases  the  fact  would  be  decidedly  significant,  and  would  aff'ord  presumptive  evi- 
dence that  the  parasitic  organism  found  bore  some  relation  to  the  morbid  process, 
but  even  if  one  and  the  same  microorganism  was  found  in  every  case  the  final  proof 
in  its  etiological  import  would  depend  upon  its  isolation  in  pure  cultures  and  the 
production  of  the  characteristic  phenomena  of  the  diseases  in  one  of  the  lower  ani- 
mals, or  in  the  absence  of  a  susceptible  animal,  in  man  himself. 

The  method  by  cultivation  is  by  far  the  most  reliable  for  the  demonstration  of  micro- 
organisms which  will  grow  in  our  culture  media,  for  isolated  cocci  or  bacilli  might 
easily  escape  observation  when  present  in  small  numbers,  but  would  serve  to  start  a 
culture.  Thus  the  bacillus  of  typhoid  fever,  which,  as  stated,  is  not  as  a  rule  found 
in  the  blood  of  the  general  circulation,  and  is  only  found  in  the  spleen  in  scattered 
clumps,  may  be  obtained  from  this  organ,  in  pure  cultures,  almost  without  fail,  by  in- 
troducing a  small  quantity  of  splenic  pulp  into  a  suitable  nutritive  medium. 

Moreover,  this  method  enables  us  to  differentiate  microorganisms  which  look  alike, 
and  which  by  microscopic  examination  alone  it  would  be  impossible  to  distinguish 
one  from  another.  This  is  a  fact  now  well  recognized  by  bacteriologists,  but  not 
generally  appreciated  by  microscopists  whose  researches  have  been  limited  to  the 
staining  and  mounting  of  sections. 

Both  methods  require  skill  and  practice  iu  the  execution,  and  great  caution  iu 
drawing  conclusions,  for  there  are  a  thousand  traps  lying  in  wait  for  the  explorer  in 
this  field  of  investigation.  It  is  for  this  reason  that  pseudo  discoveries  are  so 
numerous. 

Especial  care  is  required  in  the  microscopical  examination  of  stained  preparations 
of  yellow-fever  tissues.  One  encounters  in  the  urinary  tubules,  mingled  with  the 
debris  of  the  desquamated  epithelium,  stained  masses  of  various  forms  which  often 
closely  resemble  cocci  or  bacilli.    These  I  believe  to  be  fragments  of  nuclear  material. 


16  INTRODUCTION. 

The  same  material  is  often  massed  in  the  urinary  tubules  in  the  form  of  pings,  which 
are  deeply  stained  by  the  aniline  dyes. 

Again,  fragmentation  of  nuclei  of  cells  still  in  position  may  give  the  impression  of 
a  cell  containing  cocci,  and  the  karyokinetic  figures  found  in  the  cells,  especially  in 
the  liver,  often  resemble  bacilli  so  closely  that  it  is  difficult  to  convince  any  one  not 
familiar  with  them  that  they  are  not  microorganisms. 

The  "  plasma  cells  "  of  Ehrlich,  also,  seem  to  have  as  their  chief  function  the  role  of 
deluding  amateur  microscopists  into  the  idea  that  they  have  made  a  discovery.  They 
are  often  very  abundant  in  the  liver  and  in  the  kidney  of  yellow  fever  cases,  and  so 
closely  resemble  zoogloja  masses  of  micrococci  that  experienced  pathologists  have  been 
deceived  by  them. 

In  addition  to  these  objects  vrhich  resemble  microorganisms  there  are  dangers 
from  the  post-mortem  invasion  of  the  tissues  when  the  autopsy  has  been  delayed  be- 
yond an  hour  or  two,  in  the  warm  climates  where  yellow  fever  prevails,  or  even 
in  the  preserving  medium  or  during  the  process  of  staining. 

My  experiments  made  in  1883  showed  that  "exposure  to  9.5  per  cent,  alcohol  for  48 
hours  did  not  kill  the  bacteria  in  broken-down  beef  tea  (old  stock),"  and  pathologists 
are  familiar  with  the  picture  presented  by  the  post-mortem  invasion  of  tissues  which 
have  been  left  in  alcohol  which  was  not  strong  enough  to  preserve  them. 

Finally,  inasmuch  as  my  culture  experiments  with  material  collected  soon  after 
death  from  the  liver  and  kidney  gave  a  positive  result  in  a  certain  proportion  of 
the  cases,  it  is  evident  that  the  microorganism  most  frequently  found  by  this  method — ■ 
my  bacillus  a — should  occasionally  be  encountered  in  stained  preparations. 

The  possibility  remains  that  by  some  method  of  staining  not  hitherto  employed, 
the  specific  infectious  agent  may  yet  be  demonstrated  in  the  tissues;  but  the  fact 
that  my  culture  experiments  Avith  material  from  the  liver  and  kidney  of  ten  cases 
failed  to  demonstrate  any  such  specific  microbe  is  opposed  to  this  view.  We  may,  of 
course,  suppose  that  the  yellow  fever  germ  not  only  requires  special  methods  yet  un- 
discovered for  its  demonstration  in  the  tissues,  but  that  it  will  not  grow  in  the 
culture  media  which  I  have  employed  in  my  researches.  I  would  say  in  reply  to  this 
hypothesis  that  all  known  pathogenic  microorganisms  may  be  demonstrated  by  the 
staining  methods  employed,  and  that  inasmuch  as  the  yellow  fever  germ  appears  to 
find  a  favorable  nidus  in  filth  beds  external  to  the  body,  I  have  been  inclined  to  be- 
lieve that,  like  the  bacillus  of  typhoid  fever  and  cholera,  it  is  not  especially  nice  as  to 
the  character  of  the  medium  in  which  it  may  develop.  However,  this  may  be  a  mis- 
taken idea,  and  I  propose  in  my  future  researches  to  make  use  of  various  culture 
media  not  yet  employed,  and  especially  to  make  cultures  from  the  tissues  and  the 
excreta  in  an  atmosphere  from  which  oxygen  has  been  excluded ;  for  it  maj  be  that 
like  the  bacillus  of  malignant  oedema  and  the  bacillus  of  tetanus  the  yellow  fever 
microbe  is  anterobic. 

Inasmuch  as  some  of  the  readers  of  this  report  may  not  have  at  haud 
the  volume  in  which  the  report  of  my  investigations  in  Brazil  and  in 
Mexico  is  contained,  I  introduce  here  a  paper  read  before  the  College 
of  Physicians  of  Philadelphia  in  April,  1888,  and  published  in  the 
"Medical  News"  of  April  28,  1888,  in  which  a  summary  of  the  results 
of  these  investigations  is  given: 

Gentlemen  :  You  are  aware  that  I  have  been  engaged  during  the  past  year  in  an 
nvestigation  of  the  methods  of  inoculation  practiced  in  Brazil  and  in  Mexico,  by 
which  it  is  claimed  that  protection  against  yellow  fever  is  aff"orded.  The  subject  is 
one  of  such  great  interest  to  the  medical  profession  everywhere,  and  of  such  imiior- 
tance  with  reference  to  the  sanitary  interests  of  that  portion  of  the  United  States 
subject  to  invasion  by  the  disease  in  question,  that  Congress  provided  for  an  inves- 
tigation of  the  methods  of  inoculation  practiced  in  Brazil  and  in  Mexico,  in  the  ac$ 


INTRODUCTION.  17 

providing  for  the  civil  expenses  of  the  Government  for  the  year  ending  June  20, 
1888.  * 

Having  been  selected  by  the  President  to  make  the  investigation  referred  to,  in 
compliance  with  my  instructions  I  first  proceeded  to  Brazil  for  the  purpose  of  investi- 
gating the  methods  of  Dr.  Domingos  Freire,  of  Rio  de  Janeiro,  and  after  my  return 
from  that  country  went  to  Mexico  to  make  a  similar  research  with  reference  to  the 
value  of  the  method  of  inoculation  practiced  by  Dr.  Carmona  y  Valle.  My  detailed 
report  was  submitted  to  the  President  about  a  month  ago,  and  by  his  permission  I 
am  now  authorized  to  make  public  the  conclusions  reached.  As  I  am  about  to  go  to 
Havana  for  the  purpose  of  continuing  my  researches  with  reference  to  the  etiology 
and  prophylaxis  of  yellow  fever,  I  am  glad  to  avail  myself  of  the  kind  invitation  of 
the  College  of  Physicians  of  Philadelphia,  and  to  present  to  you,  and  to  the  profession 
generally,  the  conclusions  which  I  have  reached  up  to  the  present  date. 

These  conclusions  are  given  as  follows  in  my  report,  above  referred  to: 

"Facts  relating  to  the  endemic  and  epidemic  prevalence  of  yellow  fever,  consid- 
ered in  connection  with  the  present  state  of  knowledge  concerning  the  etiology  of 
other  infectious  diseases,  justify  the  belief  that  yellow  fever  is  due  to  a  living  micro- 
organism, capable  of  development,  under  favorable  local  and  meteorological  condi- 
tions, external  to  the  human  body,  and  of  establishing  new  centers  of  infection  when 
transported  to  distant  localities. 

"Inasmuch  as  a  single  attack  of  yellow  fever,  however  mild,  protects,  as  a  rule, 
from  future  attacks,  there  is  reason  to  hope  that  similar  protection  would  result  if  a 
method  could  be  discovered  of  inducing  a  mild  attack  of  the  disease  by  inoculation 
or  otherwise. 

"The  hypothetical  yellow  fever  germ,  multiplying  external  to  the  human  body  in 
unsanitary  places  in  tropical  regions  where  the  disease  is  endemic,  or  during  the 
summer  months  in  the  area  of  its  occasional  epidemic  prevalence,  establishes  infected 
localities,  and  susceptible  persons  contract  yellow  fever  by  exposure  in  these  infected 
areas.  We  infer,  therefore,  a  priori,  that  the  yellow  fever  germ  invades  the  system 
by  the  respiratory  tract,  by  the  alimentary  canal,  ot  from  the  general  surface  of  the 
body,  and  it  should  be  found  in  the  blood  and  tissues,  or  in  the  alimentary  canal,  or 
upon  the  surface. 

"Another  possibility  presents  itself,  viz:  That  the  germ  multiplying  in  insanitary 
localities  external  to  the  body  produces  a  volatile  poison,  which  contaminates  the 
air,  and  that  an  attack  is  induced  by  the  toxic  eftects  of  this  potent  chemical  poison. 
The  more  or  less  prolonged  period  of  incubation — two  to  five  days — in  numerous  cases 
in  which  the  attack  has  been  developed  after  removal  from  the  infected  locality, 
seems  opposed  to  this  latter  hypothesis. 

"  In  the  light  of  what  is  known  of  the  etiology  of  other  infectious  diseases,  the  hy- 
pothesis that  the  germ  really  finds  entrance  to  the  body  of  the  person  attacked  and 
multiplies  within  it,  is  that  which  presents  itself  as  most  probable,  and  it  hardly 
seems  worth  while  to  consider  any  other  unless  this  is  proved  by  a  complete  investi- 
gation not  to  be  true.  In  the  latter  event  we  would  have  to  consider  the  possibility 
of  absorption  through  the  respiratory  tract  of  a  volatile  toxic  agent,  or  through  the 
skin  of  a  poisonous  ptomaine  formed  upon  the  surface  of  the  body  by  a  specific  micro- 
organism which  does  not  itself  penetrate  to  the  interior. 

"Naturally  the  attention  of  investigators  has  first  been  given  to  a  search  for  the 
'germ'  in  the  blood  of  those  attacked,  and  in  the  blood  and  tissues  of  the  victims  of 
the  malady. 

"  The  researches  made  up  to  the  present  time  have  failed  to  demonstrate  the  con- 
stant presence  of  any  micro-organism  in  the  blood  and  tissues  of  those  attacked. 

"My  own  researches,  recorded  in  the  foregoing  report,  show  that  no  such  micro- 
organism as  Dr.  Domingos  Freire,  of  Brazil,  has  described  in  his  published  works,  or 
as  he  presented  to  me  as  his  yellow  fever  germ  at  the  time  of  my  visit  to  Brazil,  is 
found,  as  he  asserts,  in  the  blood  and  tissues  of  typical  cases  of  yellow  fever. 

4067 2 


18  INTRODUCTION. 

"  There  is  no  satisfactory  evideuce  tliat  tlie  method  of  inoculation  practiced  by  Dr. 
Domingos  Freire  has  any  prophylactic  value. 

"The  claims  of  Dr.  Carmona  y  Valle,  of  Mexico,  to  have  discovered  the  specific  cause 
of  yellow  fever  have  likewise  no  scientific  basis,  and  he  has  failed  to  demonstrate 
the  protective  value  of  his  proposed  method  of  prophylaxis. 

"It  is  highly  important,  in  the  interests  of  science  and  of  public  health,  that  further 
investigations  be  made  by  more  exact  methods,  which  have  been  perfected  since 
Drs.  Freire  and  Carmona  made  their  researches,  and  with  which  they  were  evidently 
not  familiar." 

The  failure  thus  far  to  find  a  specific  micro-organism  in  the  blood  or  tissues  makes 
it  desirable  that  a  thorough  research  should  be  made  with  reference  to  the  micro- 
organisms present  in  the  alimentary  canal,  for  it  is  possible  that  in  yellow  fever,  as 
in  cholera,  the  disease  is  induced  by  a  microorganism  which  multiplies  in  this  situa- 
tion. Additional  researches  are  also  required  before  we  can  say  definitely  that  there 
is  no  germ  demonstrable  in  the  blood  and  tissues.  Having  exhausted  our  researches 
by  the  method  of  direct  examination,  and  by  cultures  from  blood  drawn  during  life, 
it  is  highly  desirable  that  various  culture  media  should  be  inoculated  with  material 
taken,  Avith  proper  precautious,  from  the  various  organs,  and  at  the  earliest  possible 
moment  after  death,* 

I  can  not  attempt  to  give  you  in  detail,  at  the  present  time,  the  evidence  upon 
which  the  conclusions  above  stated  are  based,  but  it  is  recorded,  in  extenso,  in  my 
report  to  the  President,  and  will  no  doubt  be  published  in  due  time.  I  shall,  how- 
ever, take  advantage  of  this  occasion  to  call  your  attention  to  some  of  the  principal 
facts  upon  which  I  base  the  unfavorable  opinion  expressed  with  reference  to  the 
claims  of  Dr.  Domiugos  Freire,  of  Brazil,  and  of  Dr.  Carmona  y  Valle,  of  Mexico. 
Both  of  these  gentlemen>  as  you  are  aware,  have  laid  claim  to  priority  in  the  discov- 
ery of  the  specific  germ  of  yellow  fever,  and  both  have  practiced  inoculations  with 
material  supposed  to  contain  their  "microbe,"  having  in  view  the  production  of  a 
mild  attack  of  the  disease,  and  subsequent  immunity  as  a  result  of  this  attack. 

Dr.  Freire  has,  however,  made  a  greater  number  of  inoculations,  and  owing  to  his 
numerous  iDublications  and  very  positive  assertions  his  claims  have  received  the  most 
attention.  My  conclusion  that  these  claims  are  without  scientific  foundation  may 
seem  to  you  almost  incredible,  in  view  of  the  extended  researches  which  Dr.  Freire 
has  made  in  a  locality  where  yellow  fever  is  endemic,  and  of  the  very  favorable  sta- 
tistics which  he  has  published  in  support  of  the  value  of  his  method  of  inoculation. 
But  I  need  scarcely  remind  you  that  the  astonishing  development  of  our  knowledge 
relating  to  pathogenic  microorganisms,  which  has  occurred  during  the  past  decade, 
has  been  accompanied  by  numerous  announcements  of  psuedo  discoveries  in  this  field 
of  research,  and  that  much  confusion  has  resulted  from  the  jiremature  publication  of 
experimental  researches  made  by  enthusiastic  investigators  not  familiar  with  the 
exactions  of  modern  science,  or  with  the  exact  methods  by  which  alone  security  is 
offered  against  such  pseudo  discoveries. 

Dr.  Freire  insists  in  all  his  published  works  that  his  cryptococcus  xanthogenicus  is 
present  in  great  numbers  in  the  blood  and  tissues  of  yellow-fever  patients.  In  his 
principal  work,  Doctrine  Microbienne  de  la  fifevre  jaune,  published  in  1885,  he  makes 
the  following  statement: 

"The  microbe  xanthogenicus  is  a  cosmopolitan;  it  does  not  select  its  domicile  in 
any  organ  and  has  no  preference  for  any  organic  liquid.  "We  have  encountered  it 
with  the  same  characters,  the  same  opulence  of  proliferation,  in  the  brain,  in  the 
muscles,  in  the  liver,  in  the  spleen,  in  the  kidneys,  in  the  lungs,  in  the  blood,  in  the 
urine,  in  the  bile,  in  the  vomit,  and  even  in  the  cephalo-rachidian  fluid.     However, 

*  The  writer  went  to  Brazil  and  to  Mexico  fully  prepared  to  make  these  experi- 
ments, but,  unfortunately,  was  unable  to  secure  any  autopsies  in  either  place,  and 
the  limit  as  to  time  fixed  by  his  orders  made  it  necessary  to  return  to  the  United 
States  without  having  made  these  important  researches. 


INTRODUCTION.  19 

it  is  necessary  to  establish  a  well-drawn  distinction  as  to  the  blood;  the  blood  of  the 
general  circulation  shows  itself  much  less  charged  with  the  microbes  than  the  blood 
of  the  capillaries.  Thus,  if  I  could  admit  any  preference  on  the  part  of  the  microbe 
xanthogenicus,  I  would  say  that  it  pleases  itself  better  in  the  blood  of  the  capillaries, 
in  the  blood  which  bathes  immediately  the  anatomical  elements. 

#  ?t  ^  #  «  4  • 

"  The  occasion  seems  to  us  a  favorable  one  in  order  to  call  attention  to  some  indis- 
pensable precautions  when  the  microbes  of  yellow  fever  are  to  be  sought  in  organic 
solids  and  liquids.  While  it  is  extremely  easy  to  perceive  the  presence  of  the  microbes 
of  yellow  fever  in  the  urine  and  bile,  for  example,  by  placing  a  drop  of  these  liquids 
upon  a  glass  slide,  covering  it  with  a  thin  glass  cover,  and  examining  it  with  a  power 
of  450  to  740  or  780  diameters,  this  proceeding  can  not  be  employed  when  the  blood  is 
to  be  examined.  If  we  proceed  in  this  manner  the  globules  will  hide  nearly  all  of 
the  microbes,  and  the  observer  will  wrongfully  conclude  that  they  are  very  rare  in 
this  organic  liquid.  Not  only  does  the  form  of  the  microbe  offer  a  certain  resemblance 
to  that  of  the  red  corpuscles,  but  these  latter  in  adhering  together  envelope  the  mi- 
crobiau  cells,  and  on  the  other  hand  cast  upon  the  cells  a  jet  of  light  which  makes 
them  disappear  from  the  field  of  the  microscope. 

"But  if  we  dilute  a  little  drop  of  blood  in  a  pure  solution  of  sulphate  of  soda  and 
place  it  under  the  objective,  the  microbes  become  visible  and  will  appear  in  consid- 
erable quantity. 

"It  is  likewise  necessary  to  make  a  preparation  previously  for  the  examination  of 
the  cerebral  mass  and  of  the  muscles.  They  should  be  triturated  in  a  sterilized  mortar 
and  mixed  afterward  with  distilled  water  entirely  deprived  of  organisms,  filtered 
through  fine  linen  which  has  been  passed  rapidly  through  the  flame  of  an  alcohol 
lamp,  and  afterward  a  drop  of  the  filtered  liquid  should  be  placed  upon  a  glass  slide. 
If  we  withdraw  a  little  piece  of  brain  or  of  muscular  fiber,  even  triturated,  we  will 
not  perceive  anything  abnormal  under  the  microscope,  unless  it  be  the  anatomical 
elements  more  or  less  deformed  by  trituration. 

"It  is  not  the  same  for  the  liver.  It  suffices  to  withdraw  a  bit  of  this  organ  and  to 
crush  it  between  two  glass  slides.  Upon  observing  it  under  the  microscope  we  perceive 
at  once  a  multitude  of  microbes.  This  is  because  in  the  muscles  the  microbes  are 
lodged  between  the  fibrillEe  and  in  the  substance  which  surrounds  them ;  and  in  the 
brain  they  are  found  in  the  interior  of  the  nerve  cells,  which  must  first  be  destroyed 
by  trituration  in  order  that  their  parasitic  hosts  may  become  visible." 

Having  made  extended  researches  in  Havana  in  1879  and  during  the  past  year  in 
Brazil  and  in  Mexico,  I  am  able  to  assert  most  positively  that  no  such  microorgan- 
ism as  Dr.  Freire  has  described  is  to  be  found  in  the  blood  and  tissues  of  yellow-fever 
patients.  I  have  examined  blood  from  numerous  cases  drawn  from  the  finger  during 
life,  both  in  the  fresh  condition,  in  preparations  stained  by  various  aniline  colors, 
and  by  culture  methods,  and  I  have  studied  with  great  care  a  large  number  of  thin 
sections  of  the  liver  and  kidney,  stained  by  the  most  approved  methods,  from  a  con- 
siderable number  of  typical  cases  of  yellow  fever,  without  having  encountered  the 
cryptococcus  xanthogenicus. 

As  Dr.  Freire  asserts  that  his  microbe  is  especially  abundant  in  the  capillary  ves- 
sels, it  should  be  easily  demonstrated  in  thin  sections  of  the  various  organs,  made 
secundem  artem. 

As  a  matter  of  fact,  my  researches  show  that,  as  a  rule,  no  microorganism  demon- 
strable by  known  methods  of  staining  is  to  be  found  in  such  sections.  But  here  I 
must  state  that  in  certain  cases  microorganisms  have  been  found.  The  one  to  which 
the  most  interest  attaches  is  that  described  by  Babes.  This  was  discovered  in  1854, 
in  material  sent  to  Paris  from  the  laboratory  of  Dr.  Lacerda,  in  Eio  de  Janeiro.  At 
the  time  of  my  visit  to  Brazil  my  friend  Dr.  Aranjo  Goes  gave  me  material  from 
nine  cases,  which  had  been  j)reserved  in  Dr.  Lacerda's  laboratory  since  the  epidemic 
of  1884,  and  after  my  return  to  Baltimore  I  examined  sections  stained  by  Gram's 


20  INTRODUCTION. 

method  and  with  Loeffler's  alkaliue  solution  of  methyline  blue  from  all  of  these  cases. 
I  quote  from  my  report  as  follows: 

"In  two  of  these  cases  I  find  in  the  capillaries  of  the  liver  and  of  the  kidneys  an 
orp;anisui  which  has  been  described  by  Babes  and  by  Lacorda,  who  found  it  in  ma- 
terial collected  at  the  same  time,  and  probably  from  the  very  same  cases  as  those  in 
which  I  now  find  it.  This  organism  is  a  short  bacillus,  which  occurs  in  chains,  as 
seen  in  Fig.  2,  PI.  iv. 

"  In  certain  places,  especially  in  the  kidneys,  it  is  found  in  the  capillaries  in  great 
numbers  massed  together;  in  other  places  it  is  distributed  more  sparsely,  as  seen  in 
the  figure." 

Careful  examination  of  specimens  stained  with  Loeffler's  solution  shows  that  the 
separate  elements  in  these  little  chains  vary  considerably  as  to  their  length,  and  that 
the  ends  are  more  deeply  stained  than  the  center.  This  appearance  was  no  doubt 
observed  by  Babes,  who  first  described  the  organism  in  question,  but  he  has  inter- 
preted it  differently.     He  says  : 

"  The  filaments  appear  united  and  homogeneous  with  an  amplification  of  600  diam- 
eters, but  with  a  high  power  (l-12th  horn,  im.,  or  No.  12  of  Verick,  which  corresponds 
with  the  l-18th  of  Zeiss)  one  can  assure  himself  that  these  filaments  are  composed  of 
elliptical  grains,  almost  cylindrical,  arranged  in  pairs,  forming  little  groups,  in  which 
they  are  united  by  an  intermediary  pale  substance.  The  filaments  are  thus  composed 
of  diplococci,  or,  if  one  wishes,  of  very  short  rods  with  terminal  spores." 

Dr.  Lacerda  has  described  the  organism  referred  to  as  in  filaments  which  branch 
dichotomously,  and  believes  this  branching  to  be  a  constant  and  distinctive  charac- 
teristic of  the  parasite  which  he  accepts  as  the  veritable  yellow  fever  microbe.  He 
is  without  doubt  mistaken.  The  apparent  branching  of  the  filaments  which  he  has 
described  and  drawn,  and  which  he  showed  me  in  some  of  his  preparations  at  the 
time  of  my  visit  to  Rio,  is  due  simply  to  the  accidental  juxtaposition  of  the  torula- 
like  chains.  He  is  also  mistaken  in  supposing  that  this  organism  is  only  to  be  satis- 
factorily demonstrated  by  Gram's  method  of  staining.  My  friend  Dr.  Goes  shared 
this  belief  at  the  time  of  my  visit  to  Rio,  but  I  demonstrated  to  him  the  facility  with 
which  the  organism  may  be  stained  with  a  solution  of  methyline  blue  upon  sections 
which  he  made  for  me  from  material  in  Dr.  Lacerda's  laboratory.  Since  my  return 
to  Baltimore  I  have  made  numerous  sections  from  the  same  material  (two  cases  out 
of  the  nine),  and  find  no  difficulty  in  staining  the  organism  present  in  the  tissues 
with  methyline  blue  or  with  fuchsin.  Dr.  Goes  also  supposed  that  his  failure  to  find 
this  parasite  in  all  of  the  tissues  which  he  had  preserved  since  the  epidemic  of  1884 
Avas  due  to  the  fact  that  the  tissues  had  been  kept  too  long.  He  thought  that  it  was 
most  easily  stained  in  recent  tissues,  and  anticipated  that  when  he  had  again  an 
opportunity  to  make  autopsies  he  would  encounter  this  microorganism  in  the  tis- 
sues.    I  shall  await  with  interest  his  report  of  his  recent  researches. 

As  already  stated,  I  have  not  been  able  to  find  this  microbe  of  Babes  in  the  tissues 
of  six  undoubted  cases  of  yellow  fever  sent  to  me  from  Havana,  and  examined  most 
carefully  within  six  mouths  of  the  date  of  the  autopsies.  Babes  himself  has  renouncd 
the  idea  that  this  microorganism  bears  an  etiological  relation  to  the  disease  under 
consideration.     In  the  second  edition  of  Les  Bact^ries  he  says : 

"Since  these  researches  we  have  had  the  opportunity  to  examine  several  series  of 
sections  from  yellow  fever:  First,  the  liver  and  kidney  of  two  individuals  dead  from 
this  malady,  collected  by  Dr.  Alvarez,  were  examined  in  the  Laboratory  of  Patho- 
logical Anatomy  of  the  Faculty  of  Paris,  without  any  bacteria  having  been  found; 
second,  material  from  three  cases  of  yellow  fever  which  Koch  was  kind  enough  to 
confide  to  one  of  us.  In  these  three  last  cases,  notwithstanding  the  most  scrupulous 
research  and  notwithstanding  the  advice  of  Koch,  it  was  impossible  to  find  the  little 
chains  in  the  brain,  the  kidneys,  the  liver,  and  the  spleen.  We  must  suppose,  then, 
that  in  yellow  fever,  as  in  other  infectious  maladies,  microbes  are  oaly  found  in  the 
parenchymatous  organs  in  certain  cases,  and  not  in  all.     The  question  whether  these 


INTRODUCTION.  21 

micro-organisms  really  coastitnte  the  cause  of  the  malady,  or  simply  a  complication, 
is,  consequently,  not  resolved."     (Les  Bact^iies,  p.  528.) 

We  would  remark  that,  in  view  of  the  negative  results  attending  Bahes'  more  re- 
cent researches  and  our  own  extended  study  of  the  tissues  from  six  typical  cases 
occurring  in  Havana,  there  is  no  good  reason  for  supposing  that  the  above-described 
microorganism  bears  an  etiological  relation  to  yellow  fever.  On  the  contrary,  it 
seems  probable  that  its  presence  in  material  from  a  limited  number  of  cases  occurring 
in  Rio  is  either  entirely  accidental  or  is  due  to  a  secondary  complication,  perhaps  to 
some  form  of  septicsemia. 

From  what  has  been  said  and  from  Dr.  Freire's  own  account  of  his  method  of  trit- 
urating fresh  tissues  to  demonstrate  his  cryptococcus,  the  inference  seems  unavoida- 
ble that  in  his  researches  made  by  this  method  he  has  mistaken  broken-up  blood  cor- 
puscles and  the  granular  debris  of  the  tissue  elements  for  micri^tirganisms. 

In  his  culture  experiments  he  has,  owing  to  a  defective  technique,  encountered 
micrococci  of  various  kinds,  and  one  of  these,  which  he  brought  back  with  him  from 
Paris  iu  an  agar- agar  culture,  he  presented  to  me  as  his  yellow  fever  germ. 

I  brought  a  pure  culture  of  this  micrcroccus  with  me  to  Baltimore  and  have  culti- 
vated it  during  the  past  winter  in  various  media.  It  does  not  correspond  in  its  mor- 
phology or  mode  of  development  with  the  Cryptococcus  xanthogenicus,  as  described 
by  Dr.  Freire  in  his  various  published  works,  and,  as  stated,  is  not  found  in  the  blood 
or  tissues  of  yellow-fever  patients. 

In  his  principal  work,  published  in  1835,  Dr.  Freire  gives  the  following  account  of 
the  morphology  of  his  cryptococcus  : 

"  When  we  follow  with  care  and  attention  the  march  of  the  development  which 
characterizes  the  germs  which  produce  yellow  fever  we  acquire  the  certaintj' that, 
commencing  to  present  themselves  under  the  form  of  little  points  almost  impercepti- 
ble, they  afterward  gradually  increase  in  diameter,  until  they  attain  considerable 
dimensions;  so  that  these  little  beings,  which,  at  the  outset  had  the  aspect  of  very 
little  grains  of  sand,  not  measuring  more  than  0.001  millimetre  to  0.002  millimetre  in 
diameter,  arrive,  little  by  little,  to  such  a  development  that  they  reach  the  dimen- 
sions of  0.005,  0.007,  0.008  millimetre,  and  sometimes  even  more  in  certain  conditions. 
When  they  have  attained  the  adult  age  these  cells  are  broken  at  divers  points,  and 
discharge  their  contents,  composed  of  spores  already  formed,  mixed  with  a  viscous 
substance  of  a  yellow  color,  composed  of  a  pigment  and  protoplasmic  substance,  and 
of  the  liquids  elaborated  by  the  cells." 

Even  so  recently  as  last  year,  iu  an  address  delivered  before  the  Dosimetric 
Society  of  Paris,  Dr.  Freire  repeats  this  account  of  the  mode  of  development  of  his 
cryptococcus.     He  says : 

"Each  adult  cell  is  ruptured  in  one  or  several  points,  and  allows  the  escape  of  its 
contents,  composed  of  germs  which  are  to  perpetuate  the  species,  and  Iwo  pigments, 
one  yellow,  destined  to  infiltrate  all  the  tissues,  and  to  produce  the  icteric  color 
which  has  given  name  to  the  malady  ;  the  other,  black,  insoluble,  and  destined  to 
be  carried  along  by  the  circulatory  current,  producing  either  capillary  obstructions 
or  blood  stasis  in  the  parenchyma  of  the  organs." 

Now  this  mode  of  multiplication  is  not  known  among  the  bacteria,  and  does  not 
occur  iu  the  micrococcus  which  Dr.  Freire  placed  in  my  hands  as  his  yellow-fever 
microbe,  which  multiplies  by  binary  division  and  does  not  differ  in  its  morphology 
from  a  variety  of  microorganisms  of  the  same  class,  which  are  extremely  common  in 
all  parts  of  the  world. 

According  to  Dr.  Freire's  statement,  the  agar  culture  brought  by  him  from  Paris 
came  originally  from  the  blood  of  a  patient  with  yellow  fever  at  the  point  of  death. 

Now,  as  heretofore  stated,  I  have  demonstrated  by  the  microscopic  examination  of 
numerous  specimens  that,  when  proper  precautions  are  taken  no  microorganisms 
are  found  in  blood  drawn  from  the  finger  of  yellow  fever  patients,  and  that  no  devel- 
opment occurs  in  culture  media  inoculated  with  such  blood.     I  infer,  therefore,  that 


22  INTRODUCTION. 

the  micrococci,  etc.,  fonn'T  by  Dr.  Freire  in  his  cultures  are  due  to  the  accidental 
introduction  of  niicrooroanisms  from  without,  and  especially  from  the  surface  of  the 
linjrer  dnring  the  collection  of  the  blood.  I  may  remark  here  that  Dr.  Freire's  cul- 
tures in  li([uid  media,  which  were  made  before  he  went  to  Paris,  and  which  were 
placed  in  my  hands  for  examination,  were  all  impure,  and  contained  several  different 
micro-organisms.  I  sappo.se  that  the  micrococcus  brought  back  from  Paris  was 
isolated  while  ho  was  there  from  one  of  these  impure  liquid  cultures,  for  I  found  uo 
evidence  that  solid  culture  media  had  been  used  in  his  laboratory  in  Rio  prior  to  the 
date  of  his  visit  to  Paris. 

Nor  did  he  use,  to  any  extent  at  least,  the  well-known  methods  of  staining  bacteria 
which  are  recognized  by  bacteriologists  as  so  essential  in  the  study  of  these  minute 
micro-organisms.  This  is  shown  by  the  following  quotation  from  his  address,  de- 
livered in  Paris,  to  which  reference  has  already  been  made.     He  says : 

"  We  know  that  in  order  to  color  a  microbe  it  is  necessary  first  to  kill  it  and  then 
to  wash  the  little  microscopic  cadaver  by  means  of  reagents  possessing  the  power  of 
dissolving  all  matters  foreign  to  its  skeleton.  At  the  outset  I  applied  myself  to  the 
study  of  the  yellow  fever  microbe  in  a  fresh  state.  I  fed  it  with  the  best  food — les 
meilJeurs  engrais — for  the  purpose  of  surprising  the  different  phases  of  its  evolution 
from  its  birth  to  its  death. 

"Nevertheless,  in  fault  of  other  accusations,  some  authors  have  reproached  me 
with  not  having  colored  my  microbe.  Alas !  what  a  miserable  objection.  Is  it  neces- 
sary in  order  to  affirm  the  existence  of  a  microbe  which  swarms  by  millions  in  the 
urine,  in  the  bile,  in  the  blood,  in  the  tissues,  etc.,  is  it  necessary  to  mask  them,  to 
disguise  them  under  a  costume  of  carnival,  in  order  to  please  certain  microscopists  ? 
M.  Pasteur  has  never  colored  his  microbes,  and  nevertheless  every  one  admits  the 
existence  of  the  bacillus  of  charbon,  of  the  corpuscles  of  p^briue,  of  the  micrococcus 
of  fowl-cholera,  etc. 

"Do  not  think,  gentlemen,  that  I  fear  the  application  of  coloring  processes  to  the 
search  for  the  microbe  of  j^ellow  fever.  Far  from  it.  In  order  to  show  you  that  the 
criticism  which  I  have  just  made  is  not  due  to  prejudice,  I  will  say  to  you  that  such 
processes  have  recently  been  employed  upon  the  yellow-fever  microbe  with  complete 
success." 

A  character  upon  which  Dr.  Freire  insists,  even  in  his  address  delivered  in  Paris  in 
April,  1887,  is  the  formation  of  two  kinds  of  pigment,  one  yellow  and  one  black. 
From  the  first  he  has  affirmed  that  the  black  color  of  the  characteristic  "black  vomit" 
is  not  due  to  the  presence  of  blood  changed  by  the  acid  secretions  of  the  stomach,  as 
has  been  generally  believed  by  those  physicians  who  have  studied  the  disease,  but 
that  this  color  is  due  to  a  pigment  produced  by  his  cryptococcus.  Now,  I  have  had 
the  coccus  which  he  gave  me  as  his  j^ellow  fever  germ  under  cultivation  in  various 
media,  during  a  period  of  several  months,  and  no  black  pigment  has  been  produced. 
On  the  contrary,  the  colonies  in  Esmarch  tubes,  and  stick  cultures  in  gelatine,  or  in 
agar,  all  have  a  milk-white  color.  In  morphology  this  micrococcus  does  not  differ 
from  some  well-known  and  widely  distributed  species.  It  liquefies  gelatine  quite 
slowly,  grows  readily  at  a  temperature  of  18°  to  20°  0.  (64.4°  to  68°  F.),  and,  as  stated, 
forms  no  pigment. 

The  supposition  that  the  micro-organisms  present  in  Dr.  Freire's  blood  cultures, 
and  in  those  of  various  other  observers  who  have  discovered  yellow  fever  "germs", 
came  from  the  surface  of  the  body,  and  not  from  the  blood,  is  sustained  by  recent  ex- 
perimental researches  upon  the  sterilization  of  the  hands,  made  by  Kummell  and  by 
Furbringer. 

These  experiments  show  that  it  is  not  an  easy  matter  to  destroy  all  microorgan- 
isms upon  the  surface  of  the  body  by  means  of  a  disinfecting  solution,  and  that  a 
simple  washing  with  bichloride  solution  of  one-thousandth  does  not  usually  insure 
sterilization  of  the  hands.  Furbringer,  after  repeated  experiments,  recommends  the 
following  procedure :  (1)  Remove  all  visible  dirt  from  the  nails.     (2)  Scrub  the  hands 


INTRODUCTION.  23 

witli  soap  and  water  by  means  of  a  brnsb.  {'A)  Immerse  them  for  one  minute  in 
strong  alcobol,  at  least  80  per  cent.  (4)  While  still  wet  immerse  them  for  one  min- 
ute in  a  2  per  cent,  solution  of  mercuric  chloride. 

Less  tborough  treatment  did  not  in  Furbringer's  experiments  absolutely  insure 
sterilization.  In  the  case  of  patients  in  hospital,  the  difficulty  is  often  increased  by 
the  fact  that  their  hands  are  horny  and  begrimed  with  dirt  which  can  only  be 
removed  by  long  scrubbing. 

With  reference  to  Dr.  Freire's  experiments  upon  animals,  I  can  only  say  that  those 
performed  in  my  presence  failed  entirely  to  demonstrate  that  the  micrococcus  brought 
from  Paris  had  any  specific  pathogenic  power,  and  that  I  find  no  satisfactory  evi- 
dence in  the  record  of  similar  experiments  contained  in  his  various  publications  that 
he  has  ever  transmitted  yellow  fever  to  rabbits  or  to  guinea-pigs,  as  claimed. 

I  shall  quote  here  a  single  experiment  in  which  a  fatal  result  occurred,  and  in 
which,  as  usual,  Dr.  Freire  ascribed  death  to  yellow  fever  resulting  from  the  injec- 
tion, notwithstanding  the  fact  that  the  material  injected  (blood)  had  been  subjected 
to  a  boiling  temi^erature  for  some  minutes.  My  own  numerous  experiments  show 
that  all  known  micrococci  are  quickly  destroyed  by  a  temperature  much  below  the 
boiling  point  of  water.* 

Dr.  Freire's  account  of  this  remarkable  experiment  is  as  follows  : 

"We  must  note  that  the  microbe  of  yellow  fever  offers  a  remarkable  resistance  to 
heat.    The  following  experiment  furnishes  a  demonstration  of  this  : 

"On  the  17th  of  April,  1833,  we  subjected  to  ebullition  for  several  minutes  a 
gramme  of  blood  containing  the  microbes.  AYe  injected  it  afterward  into  a  guinea 
pig,  which  had  a  temperature  before  the  experiment  of  38.5°  C.  (101.3°  F.)  in  the 
axillary  region.     The  temperature  followed  this  mai'ch  the  following  days  : 

April  18 39°  C.  (102.2°  F.) 

April  19 39° 

April  20 39.10 

April  21 39° 

April  22 38. 7° 

April  23 37.4°  C.  (99.3°  F.) 

"The  animal  died  during  the  night  of  the  23d.  Its  autopsy  showed  the  character- 
istic lesions. 

"  It  is  necessary  to  push  the  temperature  beyond  200°  C.  in  order  to  destroy  the 
toxic  energy  of  the  microbe.  As  we  have  seen  its  virulence  resists  simple  ebullition. 
The  microscope  has  shown  that  notwithstanding  the  boiling  the  microorganisms 
retained  their  ordinary  form  and  continued  to  execute  all  of  their  movements,  a 
proof  of  their  complete  vitality."     (Ojj.  cit.,  p.  217.) 

I  may  remark  here  that  the  micrococcus  presented  to  me  by  Dr.  Freire  as  his  yel- 
low fever  germ  is  killed  by  exposure  for  ten  minutes  to  a  temperature  of  60°  C,  and 
that  it  has  no  proper  movements. 

Br.  Frtire^s  protective  inoculations. — Having  demonstrated  that  Dr.  Freire's  claim  to 
have  discovered  the  specific  cause  of  yellow  fever  is  without  scientific  foundation,  it 
may  be  thought  that  no  further  demonstration  is  required  in  order  to  show  that  his 
preventive  inoculations  are  without  value;  for  these  inoculations  are  said  to  have 
been  made  with  cultures  containing  the  attenuated  microbe  of  yellow  fever.  These 
inoculations  have,  however,  been  made  upon  so  large  a  scale,  and  the  statistical  re- 
sults, as  presented  by  Dr.  Freire,  appear  so  favorable  to  his  method  that  it  becomes 
necessary  to  analyze  these  statistics  ;  and  if,  as  he  claims,  they  establish  the  fact 
that  the  mortality  from  yellow  fever  is  very  much  less  among  those  who  have  been 
inoculated  by  him  than  among  non-inoculated  persons  exposed  in  the  same  way,  wo 
shall  be  obliged  to  concede  the  value  of  his  method,  although  the  rationale  of  the 

•  The  Thermal  Death  Point   of  Pathogenic  Microorganisms,  Amer.  Jonrn.  Med. 

Sci.,  July,  1887,  pp.  146-160. 


24  INIEODUCTION. 

protective  influence  may  not  be  apparent.  In  my  detailed  report  I  have  reviewed 
at  length  Dr.  Freire's  statistics  ia  the  light  of  the  facts  developed  by  my  personal 
researches  in  the  city  of  Rio  de  Janeiro,  where  the  inocnlatioiis  were  made.  I  can 
not  attempt  to  bring  the  evidence  before  yoa  ac  the  present  time,  and  I  have  already 
stated  to  you  my  conclusion  with  refereace  to  the  matter.  In  support  of  this  con- 
clnsion  I  shall,  however,  quote  a  few  extracts  from  my  report. 

In  1884,  Dr.  Freire  inoculated  418  persons  whose  names,  ages,  place  of  residence, 
and  length  of  residence  in  Brazil  are  given  in  an  appendix  to  his  principal  work,  pub- 
lished in  1885.  In  regard  to  the  evidence  afforded  by  these  inoculations,  I  have  writ- 
ten as  follows : 

"We  remark,  first,  that  in  selecting  foreigners  and  preferably  those  who  had  re- 
cently arrived  in  Brazil  for  his  first  experimental  test  as  to  the  efficacy  of  his  protect- 
ive inoculations,  Dr.  Freire  has  given  evidence  of  his  confidence  in  the  method  of 
prophylaxis  proposed  and  of  an  honest  desire  to  demonstrate  its  value,  and  nothing 
could  be  more  fair  than  his  full  publication  of  the  names  and  of  the  essential  facts 
with  reference  to  these  persons. 

"I  must  object,  however,  to  his  including  in  his  statistics  the  names  of  37  persons 
residing  in  Vassouras,  a  village  which  is  some  .^0  miles  distant  from  Eio  de  Janeiro. 
Even  if  these  persons  had  occasion  to  visit  Rio  during  the  epidemic  season,  as  is  stated 
by  Dr.  Freire,  it  is  probable  that  they  would  remain  as  short  a  time  as  possible,  and 
there  is  no  evidence  that  they  were  fairly  exposed  to  the  epidemic  influence.  More- 
over, if  any  of  these  persons  had  contracted  yellow^  fever  as  a  result  of  a  visit  to  Rio 
their  names  would  not  appear  in  the  mortality  list  of  this  eity,  but  in  those  of  Vas- 
souras, which  are  not  given.  The  latter  objection  applies  also  to  14  persons  among  the 
vaccinated  whose  place  of  residence  is  Nictheroy,  a  town  upon  the  bay  of  Rio  de  Ja- 
neiro, which  is  the  capital  of  the  province  of  the  same  name ;  two  persons  vaccinated 
at  Tijuca,  and  one  on  board  the  bark  Flive,  two  at  Pavina,  and  three  at  Serrai'ia  must 
also  be  excluded.  This  reduces  the  number  of  vaccinated  persons  within  the  city 
limits  to  355,  and  of  this  number  a  certain  proportion  no  doubt  left  the  city  soon  after 
being  vaccinated,  and  before  any  exposure  worthy  of  consideration  in  a  test  of  this 
kind  had  occurred." 

Dr.  Freire  admits  that  "  during  the  epidemic  season  a  great  number  of  the  vacci- 
nated were  attacked  by  the  malady,"  but  claims  that  these  attacks  were  of  a  mild 
character,  yet  he  gives  us  the  names  of  seven  vaccinated  jjersous  who  died  from  the 
disease.  This  list  has  been  added  to  by  some  of  Dr.  Freire's  confreres,  as  will  be  seen 
by  the  following  translation  of  a  letter  published  in  one  of  the  newspapers  of  Rio, 
and  bearing  date  May  5, 1887.  This  letter  is  signed  by  Dr.  Araujo  Goes,  at  present  a 
member  of  the  Central  Board  of  Health,  and  a  gentleman  whose  statements  are  worthy 
of  the  fullest  confidence: 

"  My  letter  to  the  Imperial  Academy  of  Medicine  having  been  published,  it  now 
behooves  me  to  publish  the  statistics  relating  to  the  vaccinations  on  Morro  da  Vinva. 

"One  fact  seems  tome  to  be  definitely  demonstrated,  that  is  the  woi'thlessness  of 
Dr.  Freire's  vaccination,  as  is  well  known  to  the  medical  profession  of  this  city. 

"A  year  ago  I  wrote  the  following: 

"The  want  of  skill  which  he  displayed  in  his  first  experiments,  the  false  conclu- 
sions which  he  has  drawn  therefrom,  and  the  thoughtless  precipitation  with  which  he 
has  hastened  to  make  known  incomplete  results  without  accompanying  them  with  a 
single  qualifying  remark  vitiate  all  the  methods  to  which  he  may  hereafter  resort  to 
corroborate  his  statements.     (Journal  do  Commercio,  April  20, 1883.) 

"The  mortality  among  the  persons  vaccinated  on  Morro  da  Viuva  furnishes  one 
more  proof  that  I  was  right  in  saying  this,  as  I  now  proceed  to  demonstrate. 

"There  were  A^accinated  in  this  district  60  persons. 

"  Sixteen  removed  shortly  after  the  commencement  of  the  epidemic,  and  44  re- 
mained exposed  to  its  influence.     Of  these  22  had  yellow  fever,  9  of  whom  died. 


INTRODUCTION.  25 

"The  following;  is  a  list  of  the  vacoiiiated  persons  who  had  the  fever,  the  names 
of  those  who  died  being  marked  with  an  asterisk  : 


Antonio  de  Olireira.' 

Antonio  Bento  da  Silva. 

Albino  Francisco  Maia. 

Jose  da  Silva. 

Joaquin  Pereira  da  Sonza.* 

Joaquin  Gomes  de  Azevedo. 

Joaquin  Ferreira  Tolho. 

Jose  Seabra  dos  Santos. 

Jose  de  Sonza  Ferreira. 

Jose  Gomes  de  Azevedo  Junior, 

Jose  Farinha. 


Manoel  Joaquin  Pereira  Lopes. 

Manoel  Gomes  de  Azevedo. 

Manoel  Antonio.* 

Seraphim  Goncalves  Eaynmndo. 

Manoel  Simoes.* 

Thome  Simoes. 

Manoel  da  Silva  Alves.* 

Antonio  Pereira  Neves.* 

.Joaquira  Martins  Pinheiro."* 

Joaquim  Antonio  dos  Santos  Cardoso. 


"  Consequently,  of  the  44  vaccinated  persons  who  remained  in  the  locality,  22,  that 
is  50  per  cent.,  had  the  yellow  fever. 

"  Of  the  22  patients,  9  died,  that  is  40.9  per  cent. 

"In  the  Jurnjaba  Hospital,  which  receives  scores  of  patients  already  dying  or  in 
the  third  stage  of  the  disease,  the  mortality  is  only  21  per  cent." 

After  reviewing  allot  the  evidence  obtainable  relating  to  the  inoculations  j)rac- 
ticed  in  1883  and  1834,  I  say  : 

"  The  evidence  above  recorded  seems  to  the  writer  to  be  convincing  as  to  the  com- 
plete failure  of  Dr.  Freire's  proposed  method  of  prophylaxis  as  practiced  in  1883  and 
in  1884.  We  cannot,  however,  leave  the  question  here,  inasmuch  as  a  modification 
of  the  method  was  adopted  in  1884,  and  a  large  number  of  persons  have  been  since 
inoculated  by  this  modified  method.  Dr.  Freire  says  in  his  report  under  considera- 
tion: 'I have  employed  in  nearly  all  of  the  vaccinations  the  enderraic  method,  End 
it  is  only  recently  that  I  have  injected  into  twenty  persons  the  same  cultures  by  the 
hypodermatic  method.  »  *  »  I  shall  hereafter  give  the  preference  to  the  last 
mentioned  method,  because  one  is  more  sure  that  the  liquid  employed  goes  to  exer- 
cise its  preservative  iniiuence.'  " 

In  1885  Dr.  Freire  resumed  his  inoculations  on  a  larger  scale,  but  instead  of  select- 
ing uuacclimated  strangers,  those  inoculated  were  for  the  most  part  natives  of  Brazil, 
or  Portuguese  who  had  lived  for  a  number  of  years  in  Eio  and  who  had  passed  through 
one  or  more  epidemics.  A  considerable  number  of  negroes  were  also  inoculated  and 
included  in  the  statistical  tables.  "With  reference  to  Dr.  Freire's  statistics  for  the 
year  1885  I  quote  from  my  report  as  follows  : 

"Dr.  Freire  has  omitted  to  state  one  very  important  fact  with  reference  to  the 
vaccinations  practiced  during  the  period  included  in  this  tabular  statement.  The 
date  of  the  vaccinations  is  not  given.  Fortunately  I  am  able  to  supply  this  omission 
from  his  journal  containing  the  names  of  the  vaccinated,  which  he  kindly  placed  in 
iny  hands  during  my  stay  in  Rio.  I  find  from  this  record  that  the  inoculations  were 
practiced  as  follows : 

January 392 

February 342 

March 611 

April : 139 

May 273 

Juoe 813 

Jaly •-....  481 

"  Now  it  is  well  known  that  June  and  July  are  months  during  which  yellow  fever 
does  not  prevail  in  Rio,  and  that  in  fact 'the  month  of  May  famishes,  as  a  rule,  but 
few  cases. 

"Tlie  exposure  even  in  an  epidemic  year  amounts  to  very  little  during  the  months 
of  May,  June,  and  July,  and  may  be  considered  practically  nil  in  a  year  like  1885, 


26  INTRODUCTION. 

when  the  whole  mortality  was  only  278  in  a  city  of  400,000  inhabitants.  But  Dr. 
Freire  has  included  in  his  list  1,204  persons  who  were  vaccinated  during  the  iiealthy 
winter  mouths  of  June  and  July,  and  who  presumably  had  been  exposed  during  the 
preceding  comparatively  unhealthy  m  mths  of  January,  February,  March,  and  April. 
If  these  1,291  individuals  were  protected  from  an  attack  of  yellow  fever  by  the  in- 
oculation practiced  in  June  or  July,  what  protected  them  from  being  attacked  dur- 
ing the  preceding  months  when  yellow  fever  was  prevailing  to  some  extent  ? 

"  We  remarked  with  reference  to  those  persons  selected  for  vaccination  in  1883  and 
1884  that  'in  selecting  foreigners  and  preferably  those  who  had  recently  arrived  in 
Brazil  for  his  first  experimental  test  of  the  efficacy  of  his  protective  inoculations 
Dr.  Freire  has  given  evidence  of  his  confidence  in  the  method  of  prophylaxis  pro- 
posed and  of  an  honest  desire  to  demonstrate  its  value.' 

"In  his  inoculations  practiced  in  1885  we  no  longer  find  any  evidence  of  such  selec- 
tion, and  so  far  as  we  can  judge  the  vaccinated  persons  simply  represent  the  average 
population  of  the  city  of  Rio.  It  is  well  known  that  this  population  includes  a  large 
number  of  persons  of  foreign  birth  and  especially  of  Portuguese.  The  whole  foreign- 
born  population  probably  does  not  fall  below  100,000  persons,  but  I  have  not  been 
able  to  obtain  any  exact  statistics  with  reference  to  this  point.  Dr.  Freire  vacci- 
nated 2,186  natives  and  865  foreigners.  Let  us  assume  for  the  present  that  the  1,760 
persons  vaccinated  by  him  during  the  months  of  January,  February,  March,  April, 
and  May  were  comparable,  so  far  as  the  susceptibility  to  yellow  fever  is  concerned, 
with  300,000  of  the  population  ot  Rio.  In  this  estimate  we  exclude  100,000  of  the  pop- 
ulation on  the  supposition  that  this  number  may  have  enjoyed  immunity  as  a  result 
of  having  suffered  an  attack  of  the  disease,  278  deaths  in  a  population  of  300,000  gives 
jess  than  1  death  per  1,000,  and  there  should  not  have  been  over  2  deaths  among  the 
1,780  persons  inoculated  by  Dr.  Freire  during  the  months  of  yellow  fever  prevalence. 

"Let  us  look  at  the  matter  in  another  light.  Dr.  Freire  gives  the  following  table, 
showing  the  length  of  residence  iu  Brazil  of  the  foreigners  inoculated  in  1885  : 

For  a  few  days 26 

For  a  few  mouths 71 

From  1  year  to  1  year  and  a  half 69 

Two  years 107 

Three  years 98 

Four  years 126 

Five  years 103 

On  board  ship  (de  passage) 9 

More  than  5  years 256 

Total 865 

"These  figures  also  include  the  foreigners  vaccinated  in  the  healthy  months  of  June 
and  July  and  those  temporarily  in  the  city  (a  few  days,  26,  on  board  ship,  9),  but  they 
will  serve  our  present  purpose,  which  is  to  call  attention  to  the  fact  that  759  of  the 
total  number  given  had  been  in  Brazil  (and  presumably  in  Rio)  more  than  a  year  and 
a  half  and  had  consequently  passed  through  the  preceding  epidemic  year  (1884)  with- 
out contracting  yellow  fever.  If  these  persons  resisted  yellow  fever  during  an  epi- 
demic, in  which  the  number  of  deaths  amounted  to  1,597,  how  can  it  be  claimed  that 
they  are  protected  by  a  vaccination  made  in  1885,  when,  only  237  deaths  occurred, 
scattered  about  (sporadic)  in  a  city  of  400,000  inhabitants  ?  The  same  argument  ap- 
plies with  greater  force  to  the  359  foreigners  inoculated,  who  had  resided  in  Brazil 
for  5  years  and  above  (5  years,  103,  more  than  5  years,  256).  Unless  the  list  includes 
persons  who  had  already  suffered  an  attack  of  yellow  fever,  these  individuals  had  . 
passed  through  the  epidemic  of  1880  (1,623  deaths),  as  well  as  that  of  1883  and  1884, 
without  contracting  the  disease,  and  we  can  hardly  ascribe  their  immunity  in  the 
comparatively  healthy  year,  1885,  to  Dr.  Freire'a  inoculation." 

I  pass  now  to  the  year  1886,  during  which  Dr.  Freire  inoculated  2,763  Brazilians 


INTEODUCTION.  27 

and  710  foreigners,  again  including  in  his  statistical  tables  those  vaccinated  after 
the  epidemic  season  had  passed.     In  reviewing   these  statistics  I  remark  as  follows  : 

"  We  have  quoted  this  last  report  of  Dr.  Freire  in  extenso  in  order  to  do  him  full 
jutice  by  allowing  him  to  state  his  own  case.  We  shall  now  proceed  to  show  tliat 
his  statistics  are  fallacious,  and  that  the  percentage  of  mortality  among  the  vacci- 
nated, which  he  finds  to  be  ten  times  less  than  among  the  non-vaccinated,  results  from 
a  misuse  of  the  statistical  method  and  from  a  number  of  factors,  which  are  favorable 
to  Dr.  Freire's  statistics  as  he  has  stated  them,  but  not  to  a  fair  test  of  his  method 
of  prophylaxis. 

"  In  the  first  place  we  would  call  attention  to  the  fact  that  while  during  the  com- 
paratively healthy  year,  1885,  the  immunity  among  the  vaccinated  of  that  year  is 
said  to  be  complete  (see  report  of  1885),  the  number  of  deaths  during  the  epidemic 
year  which  followed  is  stated  by  Dr.  Freire  himself  to  have  been  8.  Taking  all  of 
the  vaccinated  of  the  two  years,  and  without  making  any  allowance  for  the  consid- 
erable number  of  persons  vaccinated  who  had,  no  doubt,  left  the  city  before  the 
epidemic  of  1886  occurred.  Dr.  Freire,  with  a  total  of  6,524  vaccinated,  and  a  total  of 
8  deaths,  makes  the  proportion  one  per  thousand.  This  is  equivalent  at  the  outset 
to  an  addition  of  1,476  person  to  the  number  vaccinated,  who  being  imaginary  per- 
sons and  not  having  been  exposed  to  the  epidemic  influence  simply  aid  in  rounding 
up  the  general  percentage  of  mortality  in  Dr.  Freire's  favor  to  the  even  figure  of  one 
per  thousand.  This  is  but  one  of  many  factors  which  go  to  make  this  favorable 
showing.  Reference  to  Dr.  Freire's  MS.  journals,  which  he  kindly  placed  in  my 
hands,  shows  that  of  the  total  number  vaccinated  during  the  two  years,  4,465 
were  vaccinated  prior  to  the  epidemic  of  1866;  that  is  to  say,  before  the  Ist 
of  January,  1886.  How  many  of  these  left  the  city  before  the  outbreak  of 
the  epidemic,  how  many  were  only  temporarily  in  the  city  when  vaccinated, 
how  many  died  from  other  diseases  I  can  not  say ;  but  it  is  a  significant  fact 
that  of  the  3,051  vaccinated  prior  to  August,  1835,  Dr.  Freire  has  only  one  fatal  case 
to  report,  while  out  of  460  persons  vaccinated  in  January  and  February,  1886,  he 
reports  5  deaths,  a  mortality  of  more  than  1  per  cent.,  which  he  gives  as  the  general 
mortality  among  the  non-vaccinated.  This  is  not  apparent  from  his  own  statement 
of  the  case,  but  is  nevertheless  true,  as  I  shall  proceed  to  show.  In  his  report,  which 
we  have  just  given  in  full,  he  does  not  give  the  date  of  the  vaccination  of  these  in- 
dividuals, but  upon  referring  to  his  MS.  journals  for  1886  I  find  that  No.  3  of  his 
list,  Jos^,  son  of  Jo86  da  Costa  Vieira,  was  vaccinated  February  12,  1886 ;  No.  4, 
Paschoal  Euflfino,  on  the  6th  of  February,  1886  ;  No.  5,  Henri  Constance,  on  the  1st 
of  January,  1886;  No.  6,  Fernando  Argenteiro,  on  the  20th  of  February,  1886,  and 
No.  7,  Antonio  Saraiva,  on  the  12th  of  February,  1886.  The  same  MS.  record  for 
1886  shows  that  during  these  two  months — January  and  February,  1886 — the  total 
number  vaccinated  by  Dr.  Freire  was  460.  That  is  to  say  the  mortality  among  those 
vaccinated  during  these  two  months  was  more  than  1  per  cent.  On  referring  to 
the  mortality  list  of  the  city  for  the  same  two  mouths  I  find  the  total  number  of 
deaths  to  have  been  369,  which  in  a  total  susceptible  population  of  160,000  (Dr. 
Freire's  estimate)  would  give  a  mortality  of  1  in  436." 

Time  will  not  permit  me  to  extend  any  further  this  analysis  of  Dr.  Freire's  statis- 
tics, and  I  must  refer  you  to  my  complete  report  for  additional  details,  and  for  an 
account  of  my  personal  investigations  in  Eio  de  Janeiro.  Nor  can  I  occupy  any 
further  time  in  an  account  of  the  inoculations  practiced  by  Dr.  Carmona  y  Valle,  of 
Mexico,  and  of  his  alleged  discovery  of  the  specific  cause  of  the  disease  under  con- 
sideration. A  simple  perusal  of  Dr.  Carmona's  published  work  is  sufficient  to  con- 
vince any  competent  bacteriologist  thatowmg  to  a  defective  technique  and  inexperi- 
ence in  bacteriological  researches,  he  has  fallen  into  serious  errors  of  observation 
and  of  inference,  and  that  his  supposed  discovery  hau  no  scientific  basis. 

From  what  has  been  said,  it  will  be  seen  that  the  question  of  yellow  fever  etiology 
is  still  unsettled,  and  that  it  remains,  in  fact,  just  where  it  was  left  by  the  commis- 


28  INTRODUCTION. 

sion  sent  to  Havana  in  1879  by  the  National  Board  of  Health.  The  researches  made 
by  myself  as  a  member  of  that  commission  showed  that  in  yellow  fever  there  is  no 
microorganism  present  in  the  blood  of  the  sick  demonstrable  by  the  highest  powers 
of  the  microscope.  This  conclusion  is  supported  by  my  more  recent  researches  by 
the  method  of  cultivation.  Before,  however,  abandoning  all  hope  of  finding  a  specific 
"microbe  "  in  the  tissues,  I  desire  to  mate  cultures  from  the  various  organs,  obtained 
at  the  earliest  possible  moment  after  death.  Unfortunately,  the  opportunity  did  not 
ofter  itself  for  this  important  experiment  during  my  visit  to  Brazil  and  to  Mexico 
last  year;  but  I  hope  to  have  the  desired  opportunity  in  Havana  during  the  present 
summer,  and  shall  also  give  special  attention  to  a  search  for  the  yellow-fever  germ 
in  the  alimentary  canal,  where  it  may  possibly  be  located,  as  is  the  case  in  cholera. 
It  is  true  that  the  clinical  history  of  the  disease  does  not  especially  point  to  this 
location;  but  in  a  research  of  this  nature  it  will  not  answer  to  reject  any  possible 
hypothesis  because  of  preconceived  opinions,  and  inasmuch  as  the  present  state 
of  science  justifies  a  belief  in  a  specific  microorganism  as  the  essential  agent  in  the 
etiology  of  this  disease,  it  is  imperative  that  the  investigation  be  continued  until 
success  crowns  our  efiorts. 

In  a  report  submitted  to  the  President  in  March,  1888,  and  published 
in  the  annual  volume  of  the  Marine  Hospital  Service  for  1889,  full  de- 
tails are  given  of  my  investigations  made  in  the  City  of  Rio  de  Janeiro, 
and  those  who  desire  fuller  information  with  reference  to  Dr.  Freire's 
"protective  inoculations"  are  referred  to  this  report. 

The  summary  statement  above  quoted,  which  was  published  in  the 
Medical  l^ews  of  Philadelphia,  gave  great  offense  to  Dr.  Freire  and  led 
to  the  publication  of  a  pamphlet  entitled  "  La  Mission  de  Dr.  Sternberg 
an  Bresil,"  in  which  I  am  accused  of  incompetence,  myopia,  and  improper 
conduct  in  the  prosecution  of  the  mission  with  which  I  was  charged  by 
the  President  of  the  United  States. 

With  reference  to  my  eye-sight  I  may  say  that  I  have  never  been 
myopic,  but  that  on  the  contrary  I  v/ear  glasses  to  correct  the  presby- 
opia common  to  persons  of  my  age. 

Whether  Dr.  Freire's  other  charges  have  any  better  foundation  I 
must  leave  to  the  judgment  of  those  who  may  think  them  worthy  of 
attention. 

To  answer  the  violent  attack  which  he  has  made  upon  me  in  detail 
would  be  a  waste  of  time,  but  I  take  the  liberty  of  introducing  here  the 
postscriptum  to  my  published  report  above  referred  to,  in  which  I 
have  shown  how  little  foundation  there  is  for  his  claim  that  his  alleged 
discovery  has  been  confirmed  by  other  observers. 


POSTSCRIPTUM. 

Bai-timoee,  Sepieniber  23,  1889. 
In  his  attempt  to  neutralize  the  force  of  my  evidence  and  to  establish  his  claim  to 
have  discovered  the  specific  microbe  of  yellow  fever,  Dr.  Domiugos  Freire  has  re- 
ferred to  the  observations  of  Babes,  of  Finlay,  andDelgado,  of  Gererd  and  of  Eang6, 
as  confirming  his  own.  As  a  matter  of  fact,  the  observations  of  the  gentlemen  re- 
ferred to  give  no  support  whatever  to  this  claim,  inasmuch  as  none  of  them  have  de- 
scribed anything  corresponding  with  the  Cnjplococcm  xantlioyenicws,  or  even  with  the 
micrococcus  which  he  presented  to  me  as  his  yellow  fever  germ. 


INTKODUCTION.  29 

Thus  the  microorganism  found  by  Babes  in  material  sent  to  him  from  Dr.  La- 
cerda's  labaratory  in  Rio  de  Janeiro  is  a  short  bacillus,  arranged  in  chains,  and  not 
a  micrococcus.  Babes  himself  has  reported  his  failure  to  find  this  bacillus  in  material 
from  other  sources,  and  his  researches  show  the  absence  of  Freire's  micrococcus  in 
the  material  examined  by  him,  as  this  is  easily  stained  by  the  aniline  colors,  and  if 
present  could  not  have  escaped  the  observation  of  so  accomplished  a  microscopist 
and  bacteriologist.     In  the  second  edition  of  "Les  Bact^ries,"  Babes  says: 

"  Since  these  researches  we  have  had  the  opportunity  to  examine  several  series  of 
sections  from  yellow  fever  :  First,  the  liver  and  kidney  of  two  individuals  dead  from 
this  malady,  collected  by  Dr.  Alvarez,  were  examined  in  the  Laboratory  of  Patho- 
logical Anatomy  of  the  Faculty  of  Paris,  without  any  bacteria  having  been  found; 
second,  material  from  three  cases  of  yellow  fever  which  Koch  was 'kind  enouo-h  to 
confide  to  one  of  us.  In  these  last  three  cases,  notwithstanding  the  most  scrupulous 
research  and  notwithstanding  the  advice  of  Koch,  it  was  impossible  to  find  the  little 
chains  in  the  brain,  the  kidneys,  the  liver,  and  the  spleen.  We  must  suppose,  then, 
that  in  yellow  fever,  as  in  other  infectious  maladies,  microbes  are  only  found  in  the 
parenchymatous  orgaus  in  certain  cases,  and  not  iu  all.  The  question  whether  these 
micro-organisms  really  constitute  the  cause  of  the  malady,  or  simply  a  complication 
is,  consequently,  not  resolved." 

The  extended  researches  of  my  friend,  Dr.  Carlos  Finlay,  of  Havana,  also  give  no 
support  to  Freire's  claims  inasmuch  as  the  micrococcus  in  tetrads,  which  has  especi- 
ally engaged  his  attention  and  which  for  a  time  he  believed  to  be  the  specific  etio- 
logical agent  in  the  disease  under  consideration,  is  entirely  distinct  from  the  micro- 
coccus of  Freire.  Finlay's  Micrococcus  tetragenus  febris  flavcB,  which  I  have  called 
Microccoccus  tetragenus  versatilis,  a  name  which  heaccepts,  is  a  large  coccus  in  tetrads 
which  differs  essentially,  both  in  its  morphology  and  in  its  growth  in  culture  media 
from  the  micrococcus  of  Freire.  This  I  can  assert  most  positively,  as  1  have  had 
authentic  cultures  of  each,  given  me  by  the  gentlemen  themselves,  under  continuous 
observation  for  nearly  two  years. 

Moreover,  I  have  made  extended  culture  experiments  in  Havana  during  the  past 
two  years,  which  show  conclusively  that  neither  of  these  micrococci  is  present  in  the 
blood  of  yellow-fever  cadavers,  withdrawn  from  the  heart  or  liver  shortly  after  death. 
In  one  case  only  out  of  thirty-five  autopsies  in  which  I  have  made  cultures  from  the 
liver,  I  have  obtained  the  "tetragenus"  of  Finlay,  and  I  have  not  encountered  the 
microccocus  of  Freire  in  a  single  instance.  On  the  other  hand,  I  have  obtained  both 
of  these  cocci  in  cultures  from  the  surface  of  the  body  of  patients  in  the  hospitals 
of  Havana,  and  the  "tetragenus"  is  one  of  the  most  common  microorganisms 
encountered  in  such  cultures,  whether  made  from  the  surface  of  yellow-fever  patients 
or  those  sufi'ering  from  other  diseases. 

With  reference  to  the  observations  of  Gererd  it  is  evident  from  his  own  account 
that  if  he  encountered  micrococci  they  were  associated  with  spore-forming  filamen- 
tous bacilli,  and  that  he  was  entirely  unfamiliar  with  this  class  of  microorganisms. 
As  he  is  not  known  as  a  bacteriologist  and  has  not  given  a  detailed  account  of  his 
methods  of  research,  no  scientific  value  can  be  attached  to  his  observations.  In  a 
translation  of  his  report  made  by  Dr.  Wolfred  Nelson  and  published  in  the  Canada 
Medical  Eecord  of  J  uly,  1886,  I  find  the  following  account  of  the  morphology  of  the 
micro-organisms  encountered  by  him  : 

"In  the  month  of  June,  1882,  in  a  report  to  the  superior  agent  of  the  Interoceanic 
Canal  Company,  resident  in  the  city  of  Panama,  South  America,  I  had  the  honor  to 
inform  him  that  I  had  found  in  the  blood  of  yellow  fever  patients  some  micro- 
scopic organisms,  some  filiform,  others  resembling  a  string  of  beads  (chaplets),  and 
lastly  brilliant  little  bodies  ;  that  the  organisms  were  constant  in  appearance  and 
could  thus  serve  as  elements  for  diagnosis. 

"After  some  trials  and  a  great  many  failures,  I  succeeded  in  isolating  the  microbes, 
and  obtained  them  in  great  quantity  without  the  human  body  by  artificial  cultiva- 
tion, in  liquids  suitable  for  their  nutrition  aud  reproduction. 


30  -  INTRODUCTION. 

"I  was  then  enabled  to  study  the  mode  of  existence  of  the  microbes.  If  oue 
observes  the  filiform  bodies  attentively  for  a  given  time  he  perceives  in  their  trans- 
parent and  homogeneous  substance  a  series  of  small  corpuscles  that  reflect  light  more 
than  the  other  parts  of  the  microbe.  Little  by  little  these  corpuscles  arrange  them- 
selves around  a  central  axis  or  core,  giving  the  organism  the  appearance  of  a  string 
of  beads,  chaplet,  (This  French  word  signifies  the  string  of  beads  'told'  by  devout 
Catholics  while  praying.)  Soon  other  changes  folio ?v,  the  string-like  formation  sep- 
arates, and  in  place  thereof  nothing  remains  but  a  mass  of  brilliant  little  points. 
The  size  of  the  little  points  is  about  the  thousandth  of  a  millimetre.  These  corpuscle 
germs  have  great  resistance.  They  do  not  jyerisli  l)y  drying,  and  can  after  many  years 
serve  to  propagate  the  disease  hy  regenerating  the  filiform  bodies  luhen  placed  under  favor- 
able conditions. ^^ 

Compare  this  with  Dr.  Freire's  account  of  the  morphology  and  mode  of  develop- 
ment of  his  Cryptococcus  xantrogenicus.  In  his  principal  work,  published  in  1885, 
he  says: 

"When  we  follow  with  care  and  attention  the  march  of  the  development  which 
characterizes  the  germs  which  produce  yellow  fever,  we  acquire  a  certainty  that, 
commencing  to  present  themselves  under  the  form  of  little  points  almost  impercepti- 
ble, they  afterward  gradually  increase  in  diameter  until  they  attain  considerable 
dimensions;  so  that  the  little  beings,  which  at  tlie  outset  had  the  apiiearance  of 
little  grains  of  sand,  not  measuring  more  than  0.001"""  to  0.002"""  in  diameter, 
arrive  little  bj^  little  to  such  a  development  that  they  reach  the  dimensions  of 
0.0U5,  0.007,  O.OOS'""'  and  some  times  even  more  in  certain  conditions.  When 
they  have  attained  the  adult  age  these  cells  are  broken  at  divers  points  and 
discharge  their  contents,  composed  of  spores  already  formed,  mixed  with  a  viscous 
substance  of  a  yellow  color,  composed  of  a  pigment  and  protoplasmic  substance,  and 
of  the  liquids  elaborated  by  the  cells." 

In  an  address  delivered  in  Paris  in  1887,  Dr.  Freire  repeats  this  account  of  the  mode 
of  development  of  his  cryptococcus.     He  says  : 

"Each  adult  cell  is  ruptured  at  one  or  several  points  and  allows  its  contents  to 
escape,  composed  of  germs  which  are  to  iierpetuate  the  species,  and  two  pigments — 
one  yellow,  destined  to  infiltrate  the  tissues  and  to  produce  the  icteric  color  which 
has  given  name  to  the  malady;  the  other  black,  insoluble,  etc." 

Dr.  Rang6,  a  medical  officer  of  the  French  navy,  whose  researches  have  been  re- 
peatedly referred  to  by  Dr.  Freire  as  confirming  his  own,  says  in  his  report : 

"Unfortunately  for  our  researches  we  did  not  possess  high  powers.  I  could  not  ex- 
ceed 540  diameters,  and  I  had  no  coloring  matters  for  isolating  the  microbe  in  the 
blood  according  to  the  method  of  Ehrlich;  therefore  I  only  give  these  details  with 
reserve.  The  figured  elements  which  we  have  drawn  were  met  with  in  the  black 
vomit  of  man,  the  contents  of  the  stomach  of  guinea  pigs,  in  the  cultures  of  blood  and 
in  condensed  watery  vapor,  but  in  less  number.  They  are  agglomerations  of  cells, 
some  round  with  a  central  nucleus;  beside  these,  and  with  a  more  considerable  de- 
velopment, we  met  with  elliptical  cells  having  the  dimensions  of  a  blood  globule, 
and  with  a  nucleus  near  one  of  the  extremities  of  the  greater  diameter.  These  cells 
were  found  in  groups  of  two  or  three,  joined  by  the  extremity  containing  the  nucleus. 
This  approached  the  periphery  little  by  little ;  at  this  moment  one  observed  a  slight 
swelling,  a  sort  of  bud,  which  separated  fi'om  the  cell  which  had  given  it  birth.  Be- 
side these  elements  one  finds  others  in  the  form  of  rods,  large  and  short,  not  branched. 
These  bacilli  sometimes  contain  granules.  We  believe  that  they  come  from  the  ellip- 
tical  cells,  for  we  have  followed  under  the  microscope  the  phases  of  their  transfor- 
mation. But  the  absence  of  a  didactic  treatise,  the  absolute  absence  of  bibliographic 
resources,  prevents  us  from  making  any  positive  affirmation  with  reference  to  these 
micro-organisms." 

Notwithstanding  the  very  just  conclusion  above  reached.  Dr.  Rang6,  at  the  end  of 
his  memoir,  says : 

"In  uniting  these  various  results,  shall  we  conclude  that  there  is  a  bacillus  of  yel- 


INTRODUCTION.  31 

low  fever,  bacillus  icteroid,  and  that  it  is  possible  to  find  a  vaccine  ?  We  believe  it 
"without  affirming  it." 

The  above  quotations  will  suffice  to  show  any  well-informed  bacteriologist  that  the 
claim  of  Dr.  Freire  does  not  receive  any  support  from  the  observations  of  the  gentle- 
men mentioned,  whereas  several  competent  bacteriologists  have  reported  their  failure 
to  find  his  "cryptococcus"  or  any  other  micro-organism  in  the  blood. 

Dr.  Paul  Gibier,  who  went  to  Havana  in  the  expectation  of  finding  what  Freire  had 
described,  made  researches  by  approved  bacteriological  methods  and  reports  an  en- 
tirely negative  result.    In  a  communication  to  the  French  Academy  of  Sciences  he  says : 

"  Havana,  January  22,  1888. 

"At  the  commencement  of  the  year  1887  Dr.  Domingos  Freire,  professor  in  the 
faculty  of  medicine  of  Rio  de  Janeiro,  came  to  Paris  in  order  to  present  to  the  scien- 
tific public  his  studies  upon  yellow  fever.  M.  Fr6ire  was  presented  to  me  by  Dr. 
Rebourgeon,  who  had  studied  this  malady  with  him  in  Brazil.  The  laboratory  of 
comparative  pathology  of  the  museum  was  open  to  these  savants,  who  resumed  the 
experiments  the  results  of  which  had  previously  been  published  by  M.  Freire.  I  was 
requested  by  M.  Freire  to  examine  the  cultures  which  he  had  brought  with  him  and 
to  treat  them  by  the  new  bacteriological  methods,  which  had  not  yet  been  applied 
in  his  researches.  After  these  investigations,  made  in  common,  M.  Freire  had  the 
kindness  to  associate  me  in  a  communication  which  he  made  in  his  own  name  and 
that  of  Rebourgeon  to  the  Academy  of  Sciences  during  the  month  of  March,  1887. 

"Since,  and  as  a  result  of  this  communication,  I  received  from  the  minister  of 
public  instruction  the  mission  to  go  and  'study  yellow  fever  in  the  countries  where 
it  prevails  habitually,  and  the  prophylactic  measures  which  may  be  opposed  to  this 
malady.'  In  the  early  part  of  November,  1887,  I  disembarked  at  Havana,  where  the 
yellow  fever  still  shows  itself  at  this  epoch  in  the  so-called  sporadic  form. 

"I  give  as  succinctly  as  possible  the  results  of  my  first  investigations,  which  were 
made  in  the  hospitals  of  Havana. 

" November  16. — Among  several  cases  of  yellow  fever  I  chose  that  one  which  ap- 
peared to  me  to  be  the  most  grave  in  order  to  collect  blood  and  urine.  Fifth  day  of 
sickness:  Fever,  albuminuria,  black  vomit,  etc.     Fatal  case. 

"  November  17. — In  an  autopsy  practiced  about  8  hours  after  death,  I  collected 
blood  from  the  left  ventricle  and  from  the  right  auricle.     »     *     * 

^'November  27. — Among  several  cases  examined  I  collected,  from  the  most  severe, 
blood  and  black  vomit.     Fatal  case. 

"  December  li. — Case  in  fourth  day  of  the  disease:  Albuminuria;  coUecLed  blood, 
urine,  and  black  vomit.     Recovered. 

^' December  22. — Clinical  examination  of  a  severe  case;  Abundant  black  vomit, 
buccal  hemorrhage,  etc.;  23d,  autopsy  of  this  case  made  2  hours  after  death;  col- 
lected blood  from  the  heart.     *     *     » 

"In  order  to  avoid  useless  repetition  I  will  detail  in  a  general  way  the  methods 
pursued  in  the  examination  of  the  liquids  collected,  with  the  precautions  usual  in 
bacteriological  researches. 

"In  each  case  several  preparations  of  blood  were  examined  in  a  fresh  condition, 
then  dried  and  stained;  the  same  method  was  pursued  with  the  urine  and  the  black 
vomit. 

"Inoculations,  by  numerous  punctures,  were  made  in  agar-agar  jelly  with  blood, 
urine,  bile,  and  serum  from  the  pericardium.  »  *  *  Numerous  thin  sections  of 
the  various  organs  were  also  made ;  these  were  stained  with  a  view  to  demonstrating 
the  presence  of  microbes. 

"  Besiilts  obtained. — I  am  obliged  to  confess  here,  however  much  it  may  cost  me, 
that  my  results  contradict  in  an  absolute  manner  the  facts  advanced  bj'  M.  Domingos 
Freire,  from  whom  I  have  the  regret,  as  well  as  the  duty,  to  separate  myself. 

"The  blood. — In  a  great  number  of  preparations,  fresh  or  colored,  it  has  been  im- 
possible for  me  to  verify  the  presence  of  micro-organisms.  The  cultures,  repeated  » 
great  number  of  times^  remained  sterile. 


32  INTEODUCTION. 

'•'  The  urine,  treated  in  the  same  mauucr  as  the  blood,  has  coustantly  given  a  nega- 
tive result. 

"The  pericardial  liquid  and  the  bile,  like  the  blood  and  urine,  did  not  coutain 
micro-organisms.  I  have  found  that  even  in  the  gravest  cases  seen  by  me  the  blood 
examined  by  the  microscope  did  not  present  any  appreciable  trace  of  alteration  of 
its  elements. 

"  The  numerous  sections  which  I  have  made  of  the  different  viscera  also  have  failed 
to  show  me  the  presence  of  microbes." 

Dr.  D.  Tomayo,  of  the  bacteriological  laboratory  of  the  "Cronica  Medico-Quirur- 
gica,"  of  Havana,  has  also  reported  a  negative  result  in  his  repeated  examinations 
of  blood  drawn  from  the  finger  during  life.  His  evidence  is  valuable  both  because 
he  is  a  competent  and  conservative  bacteriologist,  having  been  instructed  in  the 
methods  of  research  in  Pasteur's  laboratory  in  Paris,  and  also  because  he  gives  a 
detailed  account  of  his  method  of  collecting  blood,  which  shows  that  he  took  ex- 
traordinary precautions  to  prevent  accidental  contamination  oi  his  cultures. 

We  quote  from  his  paper  published  in  1388  as  follows: 

'' Analysis  of  the  hlood  in  yellow  fever. — In  collecting  blood  we  have  pursued  the 
following  technique:  We  have  carefully  washed  the  finger  with  soap  and  water; 
after  that  we  have  passed  it  through  a  hole  made  in  a  piece  of  impermeable  linen  a 
foot  square;  we  have  then  washed  the  finger  with  ordinary  alcohol,  and  afterwards 
■with  a  solution  of  bichloride  of  mercury,  and  finally  with  a  mixture  of  ether  and 
absolute  alcohol.  We  have  also  washed  the  isolating  linen  with  a  solution  of  bi- 
chloride and  have  covered  it  with  a  layer  of  glycerine.  This  done  we  isolated  the  fin- 
o-er  in  a  little  glass  tube  (cloche  de  cristal),  which  had  been  washed  with  the  sublimate 
solution  and  well  heated.  By  this  complicated  technique  we  have  endeavored  to 
thoroughly  cleanse  the  skin,  to  remove  all  grease  and  every  microbe  which  might  be 
in  its  folds  and  furrows,  and  thus  to  avoid  infection  by  atmospheric  germs.  Then  we 
sterilized  a  lancet  in  the  flame  of  an  alcohol  lamp,  punctured  the  skin,  and  allowed 
the  first  drop  of  blood  which  presented  itself  to  escape,  using  only  those  drops  which 
came  later,  and  that  at  the  moment  of  their  appearance.  Following  this  proceeding 
■we  have  made  enscmeneemenfs,  either  with  the  platinum  needle  or  with  sterilized 
pipettes,  in  agar-agar  jelly,  in  peptonized  gelatine,  and  in  bouillon.  We  have  also 
examined  the  blood  collected  in  this  way  in  the  artificial  serum  of  Malassey,  filtered 
and  sterilized,  and  lastly  dried  by  the  method  of  Koch.  The  patients  from  whom 
we  obtained  blood  were  in  the  third  and  the  sixth  day  of  the  disease;  in  another 
case  the  blood  was  collected  at  the  moment  of  death.  Up  to  the  present  time  the 
cultures  in  agar-agar,  in  gelatine,  and  in  bouillon  contained  in  Pasteur  flasks  have 
remained  sterile." 

THE   MICROCOCCUS   TETRAGEXUS  FEBRIS   FLAVJE   OF   DRS.   FINLAY  AND   DELGADO. 

My  friend,  Dr.  Carlos  Finlay,  of  Havana,  is  a  most  enthusiastic  and  industrious 
investigator,  but  like  many  other  pioneers  in  bacteriological  research  at  a  distance 
from  the  centers  where  the  modern  exact  methods  had  their  origin,  at  the  time  of 
making  his  first  publications  he  was  not  familiar  with  the  methods  of  isolating  and 
diftereutiating  microorganisms,  and  fell  into  the  usual  and  almost  inevitable  errors 
of  inference  as  to  the  source  and  genetic  relations  of  the  various  microorganisms 
encountered  by  him  in  his  earlier  researches.  He  has  since  made  himself  familiar 
with  the  methods  referred  to,  and  no  longer  insists  upon  the  etiological  relation  of 
this  micrococcus  to  the  disease  under  consideration.  I  give  below  a  letter  received 
from  him  shortly  before  my  departure  from  Havana : 

"Havana,  August  29,  1839. 

"My  Dear  Doctor  :  I  send  you  a  copy  of  the  r68um6  of  our  investigations  during 

the  year.  May,  18c8-'8y,  which  Dr.  Delgado  and  myself  presented  at  the  beginning 

of  the  year.     You  wiJl  see  that  we  did  not  claim  to  have  demonstrated  that  our  tet- 

rageuus  was  the  actual  germ  of  yellow  fever,  but  merely  that  in  our  recent  investi- 


INTRODUCTION.  33 

gations  carried  out  witli  methods  which  we  deemed  to  be  reliable,  we  had  attain 
found  the  same  niicroorganisra  lu  yellow  fever  finger  blood  and  in  blister  serum, 
and  also  in  cadaveric  products  of  two  yellow  fever  autopsies.  We  likewise  ex- 
pressed the  hope  that  you  would  undertake  comparative  experiments  in  order  to 
determine,  first,  whether  it  was  a  fact  that  by  the  culture  methods  which  we  had 
described  our  tetragenus  could  be  demonstrated  in  most  of  the  products  collected 
during  life  from  yellow  fever  patients ;  and,  second,  whether  that  micro()rganism  is 
exclusively  found  in  such  patients. 

"I  am  aware  that  the  results  of  three  samples  of  yellow  fever  blister  serum  and 
seven  samples  of  blister  serum  from  accliuiated  subjects  have  given  a  negative  an- 
swer on  the  second  point.  Yet  I  can  not  wholly  divest  myself  of  the  suspicion  that 
the  greater  frequency  with  which  we  have  found  the  tetragenus  iu  our  yellow  fever 
cultures  (from  material  collected  during  life)  may  have  some  significance,  even  ad- 
mitting, as  I  do,  that  before  any  etiological  importance  could  be  claimed  for  it,  quite 
a  number  of  serious  objections  would  have  to  be  encountered,  besides  showing  that 
it  is  not  to  be  found  in  localities  where  yellow  fever  is  unknown. 

"I  remain,  my  dear  doctor,  yours  very  faithfully, 

"Caklos  Fixlay. 

"  Dr.  G.  M.  Sternberg,  U.  S.  Army,  Havana." 

As  already  stated,  I  have  found  this  "tetragenus"  of  Drs.  Fiulay  and  Delgado 
to  be  one  of  the  most  common  microorganisms  upon  the  surface  of  the  body  of  pa- 
tients in  hosi)ital  with  various  diseases,  in  Vera  Cruz  and  in  Havana.  I  also  ob- 
tained it  in  specimens  of  blister  serum  collected  by  Drs.  Finlay  and  Delgado  from  a 
case  of  brain  disease,  and  from  a  case  of  skin  disease,  both  of  which  cases  were  iso- 
lated from  any  association  with  yellow  fever  patients.  The  blister  serum  was  col- 
lected from  these  cases  and  brought  to  my  laboratory  for  the  purpose  of  making  a 
comparative  research.  I  also  frequently  encountered  colonies  of  the  tetragenus  in 
my  laboratory  in  Esmarch  tubes  which  had  been  inoculated  with  pure  cultures  of 
other  microorganisms,  showing  that  it  is  quite  a  common  atmospheric  "germ"  in 
the  City  of  Havana. 

In  a  recent  report  made  by  Assistant  Surgeon  J.  J.  Kinyoun  to  the  Supervising 
Surgeon-General  of  the  Marine  Hospital  Service  is  stated  : 

"  The  microorganism  described  by  Dr.  Ca.rlos  Finlay  (vide  London  Lancet,  Sep- 
tember 1,  1887)  has  been  under  observation  during  the  past  year. 

"Exiieriments  made  upon  various  animals  gave  no  results.  Later,  while  the 
observations  on  malarial  fever  were  under  way,  this  organism  was  discovered  upon 
the  skin  of  a  majority  of  the  patients  suffering  from  malarial  fevers,  the  patients 
hailing  from  Portland,  Me.,  to  Vera  Cruz,  Mex." 

During  the  past  year  Dr,  Freire  lias  again  resumed  his  "vaccina- 
tions" on  a  large  scale,  and  he  has  recently  jiublished  a  brochure  in 
which,  as  heretofore,  he  claims  wonderful  success  for  his  method. 

His  pamphlet  is  entitled  "  Statistique  des  vaccinations  au  moyen  des 
cultures  du  microbe  atienue  de  Ja  fievre  jaune^^  (Rio  Jauerio,  1890). 

No  doubt  some  of  those  into  whose  hands  this  pamphlet  falls  will  be 
convinced  by  the  array  of  figures  presented,  that  a  wonderful  discovery 
has  been,  made  and  that  Dr.  Freire  is,  indeed,  as  his  friends  have 
claimed,  the  Pasteur  of  Brazil.  But  when  his  statistics  are  regarded  iu 
the  light  of  the  facts  developed  during  my  visit  to  Brazil,  and  recorded 
in  my  published  report,  it  will  be  seen  that  they  have  no  scieutific 
value. 

In  the  first  place  there  has  been  no  veritable  discovery  of  the  specific 
4067 3 


34  INTRODUCTION. 

germ  of  yellon-  fever  aud  cousequeutly  there  is  no  "attenuated  virus" 
with  which  to  vacciuate.  So  long  as  Dr.  Freire's  vacciuations  were 
made  with  impure  cultures  it  was  possible  that  by  accident  the  veri- 
table yellow  fever  germ  was  present.  But  it  is  certain  that  the  micro- 
coccus which  he  preseuted  to  me  as  his  yellow  fever  microbe,  his  Cnjpto- 
coccus  xaiithogenicus,  has  uothiug  to  do  with  the  etiology  of  this  disease. 
A  careful  bacteriological  study  of  forty  cases,  made  in  Havana  since 
my  return  from  Brazil,  enables  me  to  affirm  this  in  the  most  positive 
manner.  There  is  then  no  scientific  basis  for  his  wholesale  inoculations. 
Aud,  when  his  statistics  are  considered  in  the  light  of  the  facts  hereto- 
fore referred  to,  they  give  no  substantial  support  to  his  claims. 

1  shall  consider  here  only  that  portion  of  Dr.  Freire's  latest  publica- 
tion which  relates  to  vacciuations  made  in  the  city  of  Rio  de  Janeiro. 
In  this  city  the  deaths  from  yellow  fever  are  recorded  and  published 
by  the  health  authorities,  aud  we  may  accept  the  figures  given  by 
Dr.  Freire  as  corresponding  with  the  oflncial  report:     He  says: 

Between  the  1st  of  March  aud  the  30th  of  June,  1689,  2,407  persons  died  of  yellow 
fever  (including  the  deaths  at  the  Jiirajuha  Hospital),  ^l  of  whom  had  been  vacci- 
nated; that  is  to  say  that  2,386  uon-vacciuated  persons  succumbed  to  the  disease  (1,606 
in  the  city,  800  at  Jurajuba,  in  all). 

Now  the  total  population  of  Rio  is  estimated  at  400,000.  Let  us 
suppose  that  100,000  of  this  population  enjoys  protection  from  having 
suffered  an  attack  of  the  disease;  we  have  left  300,000  persons,  who 
may  fairly  be  compared  with  those  vaccinated  by  Freire,  who  were  ex- 
j)osed  during  the  epidemic,  and  among  whom  the  mortality  was  1  in  125 
and  a  fraction  {HUi^  =  125.7). 

Among  the  2,087  "vaccinated"  there  were,  according  to  Dr.  Freire, 
21  deaths,  that  is,  1  in  99  and  a  fraction  (-ff  ^  =  99.38).  It  will  be  seen 
that  this  comparison  is  not  at  all  favorable  to  Dr.  Freire's  method. 
But  no  doubt  he  will  claim  that  the  comparison  is  unfair,  antl  that  the 
2,087  vaccinated  by  him  represent  a  greater  proportion  of  suscep- 
tible i^ersons  than  the  300,000  of  the  population  with  whom  we  have 
compared  them.  Let  us  then  deduct  another  100,000  of  the  popula- 
tion, considering  one-half  as  protected  by  a  previous  attack  or  long 
residence  in  the  city.  The  remaining  moiety  includes  all  the  foreigners 
residing  in  the  capital  city,  all  Brazilians  from  other  parts  of  the  Re- 
public, all  the  children  below  3  years  of  age,  who,  according  to  Freire, 
are  to  be  classed  with  strangers  as  to  susceptibility. 

The  ratio  of  mortality  is  now  but  little  above  that  among  the  vacci- 
nated, viz,  1  in  83  and  a  fraction  (^gS§-  =  83.78). 

But  in  this  comparison  we  have  ignored  some  very  important  factors 
which  are  in  favor  of  Dr.  Freire's  statistics.  A  large  uumber  of  the 
deaths  no  doubt  occurred  among  strangers  who  did  not  belong  to  the 
XDopulation  of  the  city,  and  especially  among  iije  sailors  on  foreign  ves- 
sels arriving  during  the  epidemic,  who  are  commonly  sent  to  the  Jura- 
juba Hosxiital  when  taken  sick.     On  the  other  hand,  we  have  no  definite 


INTEODUCTION,  35 

information  as  to  tbe  date  when  tlie  vaccinations  were  practiced,  or  the 
exposure  before  and  after  vaccination.  In  the  statistics  of  previous 
years  a  very  considerable  number  of  persons  were  vaccinated  after  the 
epidemic  had  terminated.  That  is,  persons  who  had  passed  through  tlie 
epidemic  season  without  contracting  the  disease  were  vaccinated  tind 
counted  among  those  supposed  to  be  protected  from  an  attack  by  this 
procedure.  Evidently  the  later  in  the  epidemic  the  vaccinations  were 
practiced,  the  less  value  can  be  accorded  to  the  subsequent  exjiosure 
as  a  test  of  protection.  Previous  exposure  without  being  taken  sick  is, 
on  the  contrary,  evidence  of  comparative  insusceptibility. 

To  put  those  vaccinated  on  the  same  footing  with  the  200,000  of  the 
population  of  Eio  with  whom  we  have  corajjared  them,  they  should  have 
been  vaccinated  at  the  outset  of  the  epidemic,  and  exposed  in  the  in- 
fected city  throughout  the  epidemic  season.  How  many  were  vacci- 
nated when  the  epidemic  had  commenced  to  decline,  or  after  it  had 
practically  terminated?  How  many  left  the  city  soon  after  being  vac- 
cinated ? 

These  are  questions  we  can  not  answer.  But  what  has  already  been 
said  will  suihce  to  show  that  the  results  obtained  during  the  recent 
epidemic  in  the  city  of  liio  do  not  give  any  substantial  support  to  Dr. 
Freire's  claims. 


To  give  completeness  to  this  report,  as  a  convenient  book  of  refer- 
ence, I  introduce  here  a  systematic  account  of  the  disease  to  which  it 
relates,  written  in  1888  for  Wood's  "Eeference  Handbook  of  the  Med- 
ical Sciences"  (William  Wood  &  Co.,  publishers,  56  and  58  Lafayette 
Place,  New  York).  This  article  is  reproduced  here  by  permission  of 
the  publishers. 

YELLOW  FEVER. 

DEFINITION. 

A  specific  infections  disease,  contracted  by  exposure  in  infected  localities ;  charac- 
terized by  a  single  febrile  paroxysm  of  short  dnration  (2  to  5  days),  by  the  presence  of 
albnmen  in  the  nriue,  an  icteric  color  of  the  skin,  and  a  tendency  to  passive  hemor- 
rhaoes  from  mucous  surfaces — especially  from  the  stomach— producing  "  black  vomit." 

HISTORY  AND   GEOGRAPHICAL  DISTRIBUTION. 

The  ccograiihical  range  of  yellow  fever  is  more  restricted  than  thatof  any  other  acute 
infectious  disease,  and  within  the  area  of  its  prevalence  it  is  essentially  a  disease  of 
the  littoral,  and  especially  of  seaport  cities.  While  occasional  epidemics  have  oc- 
curred upon  the  southwest  coast  of  the  Iberian  peninsula,  the  disease,  as  an  epi- 
demic, is  unknown  elsewhere  in  Europe,  and  there  is  no  evidence  that  it  has  ever  in- 
vaded the  great  and  populous  continent  of  Asia.  In  Africa  it  is  limited  to  the  west 
coast.  In  North  America,  although  it  has  occasionally  prevailed  as  an  epidemic  in 
every  one  of  our  seaport  cities  as  far  north  as  Boston,  and  in  the  Mississippi  Valley 
as  far  north  as  St.  Louis,  it  has  never  established  itself  as  an  epidemic  disease  within 
the  limits  of  the  United  States.  Vera  Cruz,  and  probably  other  points  on  the  Gulf 
coast  of  Mexico,  are  however  at  the  present  time,  endemic  foci  of  the  disease.  In 
South  America  it  has  prevailed  as  an  epidemic  at  all  of  the  seaports  on  the  Gulf  and 
Atlantic  coasts,  as  far  south  as  Montevideo  and  Buenos  Ayres,  and  on  the  Pacific 
along  the  coast  of  Peru. 

The  region  in  which  the  disease  has  had  the  greatest  and  most  frequent  prevalence 
is  bounded  by  the  shores  of  the  Gulf  of  Mexico,  and- includes  the  West  India  islands. 
Within  the  past  fetv  years  yellow  fever  has  been  carried  to  the  west  coast  of  North 
America,  and  has  prevailed  as  an  epidemic  as  far  north  as  the  Mexican  port  of  Guay- 
nias,  on  the  Gulf  of  California. 

The  idea  that  yellow  fever  may  originate  de  novo  within  the  area  of  its  occasional 
prevalence  was  entertained  by  many  medical  authors  during  the  first  half  of  the  pres- 
ent century  and  is  still  held  by  a  few.  Thus  Cornillac  (ISSG)  says:  "In  the  zone 
■which  is  habitual  to  it,  yellow  fever  may  develop  at  a  given  moment  without  appar- 
ent cause.  It  is  born  spontaneously  at  a  point  of  this  zone,  or  at  .several  at  a  time, 
and  neither  the  temiJerature,  moisture,  barometric  pressure,  electricity,  nor  finally 

36 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER,  37 

effluvia  giveu  oif  from  the  soil  can  explaiu  this  sudden  invasion."  It  is  true  tliat  in 
localities  where  the  disease  is  epidemic  cases  occur  which  are  not  directlj^  traceable 
to  importation,  but  it  is  also  true  that  in  the  principal  endemic  foci  of  the  disease, 
such  as  Vera  Cruz,  Havana,  and  Rio  Janeiro,  yellow  fever  was  at  onetime  unknown, 
and  we  have  reliable  historical  data  lixiug  the  date  of  its  importation.  In  short,  a 
careful  consideration  of  the  historical  evidence  relating  to  the  disease  gives  no  sup- 
port to  the  idea  of  independent  local  origiu,  any  more  than  in  the  case  of  smallpox, 
cholera,  or  other  specific  infectious  diseases. 

But  the  early  history  of  the  disease  is  involved  in  obscurity  and  we  are  at  present 
unable  to  determine  whether,  as  maintained  by  some,  it  was  endemic  at  certain  points 
on  the  shores  of  the  Gulf  of  Mexico  at  the  time  of  the  discovery  of  the  "  new  world," 
or  whether  it  was  imported  to  the  West  Indies  from  the  African  coast,  as  maintained 
by  others.  The  early  historians,  Herrera,  Oviedo,  Rochefort,  and  others  make  refer- 
ence to  epidemics  among  the  nati^'es,  which  occurred  prior  to  the  discovery  of  the 
Antilles,  and  to  fatal  pestilential  diseases  among  the  first  settlers  of  these  islands, 
but  their  accounts  are  not  sufficiently  exact  to  enable  us  to  affirm  that  the  disease 
referred  to  by  them  was  yellow  fever.  The  west  coast  of  Africa  was  discovered  and 
colonized  to  some  extent  before  the  discovery  of  America,  but  the  first  authentic 
accounts  of  the  prevalence  of  yellow  fever  on  this  coast  date  back  onl5"  to  the  year 
1778,  over  2  centuries  after  the  first  settlements  had  been  established.  On  the 
other  hand,  this  very  epidemic  of  1778,  at  St.  Louis  (Senegal),  was  traced  to  importa- 
tion from  Sierra  Leoue,  a  liortion  of  the  African  coast,  which,  according  to  Hirsch, 
"  appears  to  be  the  headquarters  of  the  disease  and  the  starting  point  of  its  epidemic 
inroad  into  the  territories  lying  to  the  north  and  south,  as  well  as  into  the  West 
African  islands." 

Rochefort,  whose  "Histoire  naturelle  et  morale  des  isles  Antilles  de  I'Amerique" 
was  published  in  Holland  in  1558,  says  of  the  West  Indies:  "  The  air  of  all  those 
islands  is  very  temperate  and  healthy  when  one  is  accustomed  to  it.  The  pesie  was 
formerly  unknown  there  as  well  as  in  China  and  other  places  in  the  Orient ;  but  some 
years  since  the  islands  were  afdicted  with  malignant  fevers,  which  the  physicians 
considered  contagious.  The  bad  air  was  brought  there  by  some  ships  which  came 
from  the  coast  of  Africa,  but  at  present  we  hear  nothing  more  of  these  maladies." 

It  seems  very  probable  that  a  pestilential  malady  which  prevailed  for  a  time  in 
these  usually  healthy  islands  and  then  disappeared,  was,  in  fact,  yellow  fever,  and 
that  it  was  introduced  by  ships  from  the  west  coast  of  Africa  is  not  at  all  incredible. 
Indeed,  it  almost  seems  necessary  to  look  for  an  original  endemic  focus  of  the  disease 
outside  of  the  West  Indies,  for  the  reason  that,  in  the  comparatively  few  places  where 
it  is  now  endemic,  there  is  historical  evidence  to  show  that  there  was  a  first  importa- 
tion aud  a  previous  period  of  exemption;  while,  on  the  other  hand,  the  conditions 
npou  which  endemicity  at  the  present  day  seems  mainly  to  depend,  were  formerly 
unknown — conditions  arising  from  the  aggregation  of  population  at  seaport  cities, 
as  at  Havana,  Vera  Cruz,  and  Rio  Janeiro. 

Some  authors  have  attempted  to  identify  the  epidemic  disease  mentioned  by  Hum- 
boldt—called  by  the  natives  "  Matlazahuatl " — which  prevailed  in  Mexico  in  1545. 
1576,  1736-37,  and  1761-'62,  with  yellow  fever;  but  as  pointed  out  by  Hirsch,  this 
disease  prevailed  almost  exclusively  among  the  natives  of  the  interior  and  of  the 
table-land  of  Mexico,  while  yellow  fever  is  essentially  a  disease  of  the  littoral. 

Coruillac,  a  recent  French  author,  who  has  made  a  careful  study  of  the  sanitary 
history  of  the  West  Indies,  as  contained  in  the  works  of  Oviedo,  Herrera,  Gomara, 
aud  other  Spanish  authors  of  the  sixteenth  century,  arrives  at  the  conclusion  that 
the  x>estilential  disease  from  which  the  settlers  in  the  first  Spanish  coloay  at  Nueva- 
Jsabella,  and  at  Santo  Domingo  (1494-1514),  are  said  to  have  suftered,  aud  which  was 
characterized  by  a  "saffron-yellow"  color  of  the  skin,  was,  in  truth,  yellow  fever. 
While  it  apiiears  quite  probable  that  this  was  so,  we  can  not  accept  it  as  demon- 
strated, as  the  first  authentic  accounts  of  yellow  fever  in  the  West  Indies  date  from 
about  the  middle  of  the  following  century. 


38  ETIOLOGY    AND    PREVENTION    OF    VELLOW    FEVER. 

In  163o  a  French  colony  was  establislied  nijon  the  island  of  Guadalupe,  and  shortly 
after  their  arrival  a  pestilential  disease  apjieared  auiono;  the  colonists  which,  from 
the  account  given  by  Dutertre,  a  Catholic  X'l'iest  who  came  to  the  island  5  years 
later,  is  accepted  by  Hirsch  and  by  Coruillac  as  having  been  yellow  fever.  From 
Dntertre's  account,  however,  as  quoted  by  Coruillac,  it  would  appear  that  yellow 
fever  was  first  imported  into  the  island  of  Guadalupe  in  the  year  1648,  and  that  the 
great  mortality  previously  reported  was  due  to  other  causes.  Dutertre  says :  "Dur- 
ing this  same  year  1648,  the  ])cste,  until  then  unknown  i)i  these  islands  since  they 
were  inhabited  by  the  French,  was  brought  there  by  some  vessels.  It  commenced  at 
Saint  Christophe,  and  during  the  18  mouths  that  it  lasted  carried  away  nearly  one- 
third  of  the  inhabitants.  This  ej)idemic  peste  caused  in  those  who  were  attacked  a 
violent  mal  dc  tetc,  great  debility  in  all  the  members,  and  continual  vomiting,  so 
that  in  3  days  it  put  a  man  in  his  tomb.  This  contagious  malady  was  brought  to 
Guadalupe  by  a  ship  from  La  Rochelle,  called  Le  lia'uf." 

At  Barbadoes  the  disease  may  have  prevailed  for  some  years  prior  to  its  introduc- 
tion to  Guadalupe,  but  the  first  authentic  account  relates  to  the  year  1647.  Richard 
Ligon,  who  arrived  at  the  island  in  the  month  of  September  of  this  year,  says  that 
the  city  of  Barbadoes  was  at  that  time  suftering  from  a  scourge  which  caused  great 
ravages,  so  that  the  living  scarcely  sufficed  to  bury  the  dead.  According  to  this 
author,  the  cause  of  the  epidemic  was  unknown ;  it  was  uncertain  whether  it  had 
been  iihported,  or  whether  it  originated  from  bad  food,  the  use  of  marsh  water,  and 
the  intemperance  of  the  colonists.  Ligon  inclines  to  attribute  it  largely  to  the  latter 
cause,  and  remarks  that  not  more  than  one  woman  died  for  every  ten  men.  We  may 
safely  assume,  from  the  subsequent  history  of  the  island  of  Barbadoes,  that  the  epi- 
demic plague  referred  to  by  Ligon  was  not  of  local  origin,  for  with  a  rapidly  inci'eas- 
ing  population  this  island  has  enjoyed  considerable  periods  of  immunity  from  yellow 
fever,  and  when  epidemics  have  occurred  they  have,  as  a  rule,  been  clearly  traced  to 
importation.  From  this  time,  1647-'4ii,  the  history  of  yellow  fever  in  the  West  Indies 
is  a  history  of  epidemic  outbreaks  at  varying  intervals  at  the  principal  seaport  towns, 
traced  sometimes  to  importation,  but  more  commonly  assumed  to  be  of  local  origin. 
It  was  epidemic  in  Jamaica  in  1655,  and  again  in  1671;  at  Santo  Domingo  in  1656; 
at  Martinique  in  16S3  and  1696.  In  1699  it  prevailed  widely  as  an  epidemic  in  the 
West  Indies,  and  according  to  Hinemann  made  its  first  appearance  at  Vera  Cruz,  the 
principal  seaport  on  the  Gulf  coast  of  Mexico. 

Cuha. — I  can  not  attempt  to  follow  here  the  history  of  yellow  fever  in  the  West 
Indies  generally,  but  shall  give  an  account  of  its  prevalence  in  Havana,  as  this  is 
now  an  endemic  focus  of  the  disease,  and  the  point  which  is  the  most  dangerous  to 
the  UnitedStates,  on  account  of  its  proximity  and  the  constant  commercial  intercourse 
between  this  city  and  our  own  seaports. 

The  historian  Pezuela  records  the  prevalence  of  a  malignant  pestilential  disease 
in  Havana  in  1648,  a  year  in  which,  as  we  have  seen,  yellow  fever  was  epidemic 
in  the  islands  of  Guadalupe  and  of  Barbadoes.  He  says:  "In  this  year  there  occur- 
red in  Havana  a  great  i^est  of  putrid  fevers  which  remained  in  the  port  almost  all 
summer.  A  large  part  of  the  garrison  and  a  larger  part  of  the  crew  and  passengers 
in  the  vessels  died." 

The  epidemic  continued  the  following  year,  and  in  1653-'54,  according  to  the  author 
above  quoted,  "the  epidemic  was  renewed  with  equal  fury  ;"  and  in  1655  "in  the 
capital  continued  to  carry  away  its  victims  without  regard  to  rivalries  and  passions." 
According  to  Dr.  S.  E.  Chaille,  i)resident  of  the  Havana  yellow  fever  commission 
(1879),  from  whose  report  we  have  quoted  the  above  extracts  from  Pezuela,  there  is 
no  historical  evidence  of  the  prevalence  of  yellow  fever  in  Havana  for  more  than  a 
hundred  years  after  the  date  mentioned.  "On  the  contrary,  there  are  repeated 
records  of  the  great  salubrity  of  the  climate  and  the  absence  of  epidemic  diseases." 

It  was  not  until  the  year  1761  that  yellow  fever  established  itself  in  the  previously 
healthy  city.  Pezuela  gives  the  following  account  of  its  introduction  :  "  Although 
Havana  is  situated  on  the  northern  boundary  of  the  torrid  zone,  it  was  very" justly 


ETIOLOGY    A'^fD   PREVENTION    OF    YELLOW   FEVER. 


39 


considered  one  of  tlie  most  healthy  localities  on  the  island  hefore  its  invasion  in  a 
Xiermaneut  manner  by  the  vomito  negro,  imported  from  Vera  Cruz  in  the  summer  of 
1761.  *  *■  *  In  May  there  came  from  Vera  Cruz,  with  materials  and  some  prison- 
ers destined  for  the  works  on  the  exterior  fortifications  of  Havana,  the  men-of-war 
Reina  and  America,  which  communicated  to  the  neighborhood  the  epidemic  known 
by  the  name  of 'vomito  negro.'  At  the  end  of  the  following  June  there  were  sta- 
tioned in  this  port  nine  men-of-war,  despatched  from  Cadiz,  and  sent  to  the  chief  of 
tlie  squadron,  Don  Entienne  de  Hevia ;  they  brought  a  reinforcement  of  2,000  men 
More  than  3,000  persons  succumbed  to  the  epidemic  on  this,  the  first  appearance  of 
the  vomito." 

From  this  time  to  the  present  day  the  new  levies  of  troops  sent  from  Spain  to  Cuba 
have  continued  to  suffer  enormous  losses  from  the  endemic  pestilence.  In  1779  there 
arrived  from  Spain,  then  at  war  with  Great  Britain,  "an  array  of  3,500  men,  which 
was  immediately  decimated  by  the  vomito."  In  1780,  during  the  month  of  August, 
an  army  of  8,000  men  was  landed  in  Havana,  which  during  the  two  following  months 
suffered  a  loss  of  about  2,000  men  with  the  vomito.  Pezuela  records  the  fact  that  in 
1794,  in  the  garrison  and  squadron,  there  were  more  than  1,600  victims  to  the  disease. 

The  endemicity  of  yellow  fever  in  Havana  was  fully  established  by  the  researches 
of  the  commission  sent  to  that  city  in  1879,  by  the  national  board  of  health.  Dr. 
Chaille,  president  of  this  commission,  says  in  his  elaborate  report,  published  in  1881: 
"Since  1761,  yellow  fever  has  prevailed  certainly  in  Havana,  and  i)robably  in  other 
places  in  Cuba,  every  year,  and  the  dates  of  prevalence  recorded  in  our  text-books 
indicate  no  more  than  the  years  of  greatest  prevalence.  The  disease  prevails  in 
Havana,  and  in  some  other  places  in  Cuba,  not  only  evevy  year,  but  also  every  month 
in  the  year;  records  in  1837  indicate  that  at  that  date  the  monthly  prevalence  had 
become  habitual  in  Havana  ;  the  statistics,  solely  of  the  military  and  civil  hospitals, 
prove  that  during  the  408  months,  1856-79,  there  was  only  one  single  month  free  from 
an  oflicially  recorded  case  of  yellow  fever." 

The  following  tables  are  from  the  "Preliminary  Report  of  the  Havana  Yellow 
fever  Commission  : " 

Monthly  maximum  and  minimum  deaths  hy  yellow  fever  in  Havana  during  the  10  years 

1870-79, 


Months. 


Jiimiary. 
February 
March... 

April 

May 

Jiino 


Mini- 

Maxi- 

mum. 

mum. 

6 

32 

4 

24 

4 

32 

4 

37 

13 

103 

66 

378 

•        1 

Months. 


July 

August 

September 
October  ... 
ISToveniber 
Decemher. 


Mini- 

M 

ixi- 

mum. 

muiu. 

68 

675 

70 

416 

35 

234 

28 

185 

5 

150 

9 

82 

In  no  one  of  the  10  years,  1870-79,  has  there  ever  been  fewer  deaths  than  in  the  first, 
nor  more  than  in  the  second,  column.  The  total  deaths  by  yellow  fever  for  each 
year  were  as  follows : 

Total  deaths  hy  yellow  fever  in  Havana. 


In  1870 665 

In  1871 901 

In  1872. 515 

III  1.S7:! 1,241 

In  V874 1,425 


In  1875 1,0111 

In  1876 1,019 

In  1877 1.374 

In  187S l,5.-.0 

In  1879,  to  October  1 1,353 


'  Matanziishas  the  repntatiou  of  having  long  suffered  annually  with  yellow  fever; 
the  earliest  positive  date  secured  by  me  was  reported  by  Dr.  Gniteras,  a  member  of 
the  commission,  a  native  of  Matanzas,  who  was  assured  bj'  one  of  the  oldest  physi- 


40 


ETIOLOGY    AND    PREVENTION    OF   YELLOW    FEVER. 


cians  that  the  citysnftered  with  the  disease  in  1823,  wheu  he  came  to  Matauzas,  and 
it  has  ijrerailed  everj- year  since."     (Chaille,  op.  elf.). 

Cienfuef/os. — "  Yellow  feverevery  year  since  1850,  except  in  1862  and  1874." 

Sanliago  de  Cuba. — "  Yello^v  fever  i)revailed  every  year,  and  nearly  every  mouth, 
from  1850  to  the  present  time." 

Manzanillo. — "  Yellow  fever  every  year  since  1866." 

Vera  Cruz,  the  principal  seaport  on  the  Gulf  coast  of  Mexico,  is  also  tlie  principal 
endemic  focus  of  yellow  fever  npon  this  coast.  According  to  Hineniauu,the  first  epi- 
demic occurred  in  1699,  a  year  in  which  yellow  fever  was  widely  prevalent  in  the 
West  Indies,  and  in  which  it  x>revailed  for  the  first  time  as  anej)idemic  in  the  city  of 
Philadelphia. 

The  following  table,  which  I  copy  from  a  paper  by  Dr.  Zacarias  R.  Molina,  a  med- 
ical oiificer  of  the  Mexican  Army  who  has  for  a  number  of  years  been  on  duty  in  the 
military  hospital  at  Vera  Cruz  shows  the  continued  prevalence  of  the  disease  in 
that  city  during  a  period  of  nearly  16  years : 

Mortality  from  yellow  fever  in  the  city  of  Vtra  Cruz  from  July,  1867,  to  Decemher,  1881. 


Months. 

18G7. 

1868. 

1869. 

1870. 

1871. 

1872. 

1873. 

1874. 

1875. 

1876. 

1877. 

1878. 

1879 

1880. 

1881 

7 

6 

7 

31 

42 

16 

28 

21 

21 

9 

2 

3 

3 

2 
2 
4 
5 
14 
45 
53 
39 
29 
11 

6 

210 

1 

3 
1 
19 
59 
59 
74 
20 
10 
7 

1 
2 

2 

3 
11 
24 

7 
12 
11 

6 

79 

7 

2 

4 

11 

29 

93 

118 

105 

41 

13 

2 

425 

16 
5 

6 

4 
2 

1 
1 
1 
2 
1 
3 

21 

2 

1 
1 

1 

3 

9 

42 

92 

98 

219 

28 

1 
1 

1 

22 

2 

.... 

1 

6 

19 

113 

71 
17 
10 
15 
2 
4 

271 

29 

April   

1 

7 

58 

114 

110 

62 

45 

24 

7 

444 

29 

ilav 

2 
4 
7 
9 
6 
1 
3 

4 

7 

54 

144 

104 

77 

50 

27 

528 

94 

1 
1 

933 

July 

8 
29 
36 
17 
11 

8 

109 

132 
39 

S^i)tembc-r 

October 

22 

1 

2 

« 

3 

5 
2 

25 
18 

4 

Total 

193 

7 

10 

223 

34 

675 

There  is  no  evidence  of  continued  j)revalence  at  other  towns  upon  the  Mexican 
coast,  but  epidemics,  which  have  usually  been  traced  to  importation  from  Vera 
Cruz,  have  occurred  at  Matamoras  (1858,  1S63,  1867);  at  Tampico  (1821,  1836,  1845, 
1847.  1853,  1864);  at  Tuxpan  (1S63,  lc75,  1877);  at  Campeclie  (1865,  1877);  and  at  Man- 
zanillo (1868). 

The  Gulf  coast  of  South  America,  and  especially  the  English  and  French  settle- 
ments in  Guiana,  have  been  frequently  visited  by  epidemics  of  yellow  fever,  and  it 
is  probable  that  the  disease  is  endemic  at  one  or  more  points  upon  this  coast.  Its 
epidemic  prevalence  is  recorded  for  the  following  years  at  Devierara:  1793-96,  1800, 
1803,  1818,  1819,  1820,  1821,  1825,  1827,  1828,  1831,  1837-'39,  1841-'45,  1851-'53,  1861-'66 
(Hirsch). 

In  Venezuela  the  disease  has  prevailed  at  the  capital,  Caracas,  and  the  neighboring 
seaport,   La  Guayra,  in  the  years  1693,  1696,  1793,  1797,  1802  and  1869. 

In  Central  America  epidemics  have  occurred  at  all  of  the  principal  seaports  :  Panama 
1740,  1858,  1859,  1867  ;  Fortohello,  1726,  1729,  1740,  1793,  1860,  1866,  1867 ;  Belize,  1860; 
Xicaragua,  1868. 

Brazil. — The  Portuguese  author.  El  Hastio  da  Eocha  Pilti,  has  given  nn  account,  in 
his  "History  of  Portuguese  America,"  published  in  Lisbon  in  the  year  1730,  of  aii  epi- 
demic malady  which  prevailed  in  Peruambuco  in  the  year  1686,  which  very  probably 
was  yellow  fever.  This  author  says  (Book  Vll.,  \).  427  et  seq.) :  "In  the  year  1686, 
commenced  in  Peruambuco  that  terrible  plague  (contagious  disease,  Bicha)  which 
must  be  attributed  to  the  sins  of  the  population  of  these  provinces,  corrupted  by  the 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER. 


41 


vices  into  which  they  were  enticed  by  the  wealth  and  freedom  of  BraziL  Many 
causes  are  alleged,  the  most  worthy  of  attention  being  the  arrival  of  sonic  barrels  of 
meat  which  returned  from  the  island  of  Sao  Thome  (St.  Thomas).  These  were 
opened  bjr  a  cooper,  who  shortly  afterward  fell  dead.  Soon  after  sevei'al  persons  of 
his  family,  to  whom  he  had  communicated  the  disease,  also  died.  The  epidemic 
spread  to  such  an  extent  among  the  iuhabitauts  of  Recipe  (Peruambuco)  that  the 
mortality  exceeded  2,000,  which  was  very  large  in  proportion  to  the  population. 
Thence  the  disease  extended  to  Olinda  and  its  vicinity,  and  very  few  were  the  per- 
sons who  escaped  it,  such  wore  its  virulence  and  intensity."  The  account  given  by 
the  historian  of  the  clinical  features  of  this  pestilential  disease  is,  of  course,  very 
imperfect,  but  it  seems  to  justify  the  belief  that  the  disease  was  really  yellow  fever. 

The  highest  medical  authorities  in  Brazil  agree  that  yellow  fever  was  not  endemic 
in  the  principal  seaports  of  the  Empire  prior  to  the  year  1849,  when  it  was  introduced 
to  the  city  of  Bahia  by  the  North  American  brig  Brazil,  which  sailed  from  New 
Orleans,  where  yellow  fever  was  prevailing,  and  touched  at  Havana.  Two  of  the 
crew  of  this  brig  died  of  yellow  fever  during  her  voyage  from  the  latter  port  to 
Bahia.  Soon  after  her  arrival  the  disease  made  its  appearance  among  those  who  had 
communicated  with  the  ship,  and  later  on  other  vessels  in  the  harbor.  The  first 
case  occurred  a  few  days  after  the  arrival  of  this  brig  (November  .3).  A  part  of  her 
cargo  is  said  to  have  consisted  of  little  barrels  of  beef  which  had  become  putrid. 
From  Bahia  the  disease  was  carried  to  Rio  Janeiro,  where  during  the  epidemic  season 
of  1850  it  caused  a  mortality  of  4,1G0. 

According  to  Professor  Barata,  of  the  faculty  of  medicine  of  Rio  Janeiro,  yellow 
fever  continued  to  prevail  m  Brazil  until  the  year  1861,  when  it  disappeared  for  8 
years,  to  reappear  in  1869-'70.  as  the  result  of  a  fresh  importation.     The  Italian  ship 
Creolla  del  Plata,  which  had  touched  at  St.  lago,  where  yellow  fever  was  prevailing- 
is  named  as  the  vessel  which  introduced  the  disease  on  this  occasion. 

The  mortality  from  the  disease  under  consideration  in  the  city  of  Rio,  from  the 
time  of  its  introduction  in  1850  to  a  recent  date,  is  shown  by  the  followino-  table : 

Mort.ility. 

4,160 

475 


1850 
J  851 
1852 
185:5 
1854 
1855 

18.:g 

1857 
1858 
1^59 
1860 
1861 
]86-> 
1-63 
1864 
1865 
1866 
1867 
1868 


1, 943 

853 

21 

0 

0 

1,425 

800 

500 

1,249 

247 

12 

0 

0 

0 

0 

0 

0 


Mortality. 

1869 274 

1870 1,117 

1871 8 

1872 102 

1873 3,659 

1874 829 

1875 1.292 


J876 
1877 
1878 
1879 
1880 
1881 
1882 
1883 
1884 
1885 
1886 


3,  317 
282 

1, 174 
974 

1.433 

219 

95 

1,  3.36 
618 
278 

1.  397 


In  18.55  yellow  fever  is  said,  by  Hirsch,  to  have  prevailed  extensively  in  Brazil, 
although  this  was  not  an  epidemic  year  in  Rio  Janeiro.  The  following  year  it  ex- 
tended along  the  Amazon  far  into  the  interior  of  the  country.  The  years  of  greatest 
e])idemic  prevalence  since  that  date  have  been  1859-60, 1862,  1869-'70,  1872-'73,  1875- 
'77  (HirscL). 

From  Brazilian  ports  the  disease  has  occasionally  been  introduced  to  the  cities  at 
the  mouth  of  the  Rio  de  la  Plata,  and  has  there  caused  great  loss  of  life.     The  first 


42      ETIOLOGY  AND  PEEVENTION  OF  YELLOW  FEVER. 

epidemic  at  Monicvideo  was  in  1857,  and  it  was  again  introdnced  into  this  city  from 
Peruaoibuco  iu  1872.     It  prevailed  in  the  city  of  Bikvos  Ayrea  in  1858  and  in  1870. 

Yellow  fever  is  said  to  have  been  convoyed,  to  the  Pacific  coast  of  South  America  by 
a  party  of  German  emigrants,  who  laudefl  at  ('allao,  rem,  in  1854.  The  disease  spread 
from  this  port  to  the  capital,  and  in  the  course  of  the  next  2  or  3  years  to  the  princi- 
pal towns  upon  the  Peruvian  coast,  where  it  continued  to  prevail  up  to  the  year  1860. 

ChUi,  np  to  the  present  time,  has  remained  exempt  from  the  disease  (Hirsch). 

Upon  the  u-cst  coasi  of  Jfrica  the  headquarters  of  yellow  fever  is  that  portion  of  the 
coast  which  belongs  to  the  province  of  Sierra  Leone,  and  epidemics  at  other  points 
upon  the  African  coast  have  frequently  been  traced  to  this  locality.  It  seems  very 
doubtful,  however,  whether,  as  some  authors  suppose,  this  is  really  the  original  source 
of  the  disease.  The  French  authors,  Berenger-Feraud  and  Bourru,  both  call  atten- 
tion to  the  fact  that  we  have  no  account  of  the  disease  jirior  to  the  year  1778,  although 
the  African  coast  was  discovered  and  colonized  long  before  the  discovery  of  the 
West  Indies  ;  and  that,  on  the  other  hand,  the  early  settlers  in  these  islands  suffered 
from  a  pestilential  malady  which  very  probably  was  yellow  fever. 

At  St.  Louis  (Senegal)  an  epidemic  occurred  in  1778  and  this  is  the  first  outbreak 
of  the  disease  of  which  we  have  any  reliable  information  in  this  portion  of  the 
world.  The  disease  in  this  instance  is  said  by  Schotte  to  have  been  imported  from 
Sierra  Leone,  where  epidemics  are  recorded  to  have  occurred  daring  the  present  cen- 
tury iu  1816,  1823,  1825,  1829-'30,  1837-':!9,  1845-'47,  1859,  1862,  1864,  1865-'66,  1868, 
1878  (?)  (Hirsch).  Frequent  epidemics  have  also  occurred  at  S&negamhia,  and  the 
disease  has  prevailed  upon  the  Gold  Coast  (18.52,  1857,  1862),  the  Congo  Coast  (1816, 
1860,1862,1865),  at  the  Ca^je  Verde  Lslands  (1845,  1862,  1>'CS),  and  the  Canary  Lslands 
(1701, 1771,  1810, 1846, 1862). 

Iu  EUROPK  the  ravages  of  jcllow  fever  have  been  restricted  mainly  to  the  Iberian 
peninsula.  This  is  due,  no  doubt,  to  the  frequent  intercourse  between  Spain  and 
Portugal  and  the  West  Indian  ports,  in  which  the  disease  is  most  prevalent,  and  to 
the  fact  that  the  summer  temperature  of  these  countries  is  favorable  for  the  epidemic 
extension  of  the  disease,  whereas  the  more  northern  portions  of  Europe  are  practically 
outside  of  the  yellow  fever  zone. 

The  first  epidemic  in  Spain  occurred  in  the  year  1700,  at  Cadiz.  This  city  also 
suftered  in  1730-'31,  17.'^3-'34,  1764,  1780,  1800,  1S04,  1810,  1819-'21.  The  epidemics  of 
IFOO,  1810,  and  1819  were  not  limited  to  the  city  of  Cadiz,  but  the  disease  extended 
to  the  interior  and  caused  a  considerable  loss  of  life  in  the  provinces  of  Granada  and 
Adalusia,  and  also  in  some  of  the  towns  of  Murcia  and  Catalonia — especially  in  Bar- 
celona, from  which  city  the  disease  was  conveyed  to  the  island  of  Majorca  during 
the  last  epidemic.  No  wide-spread  epidemic  has  occurred  in  Spain  since  1821,  but 
local  outbreaks,  as  a  result  of  importation  from  the  West  Indies,  have  occurred  in 
Gibraltar  (1828),  Barcelona  (1870),  and  Madrid  (1878). 

The  first  epidemic  at  Lisbon  was  in  1723,  a  second  was  inaugurated  in  1*56,  and 
during  the  following  year  developed  into  a  devastating  scourge  which  extended  to 
the  towns  of  Belem,  Olivfes,  and  Almada. 

In  Italy  yellow  fever  has  only  once  eflected  a  temporary  lodgement,  at  Leghorn,  in 
1804,  where  it  was  imported  from  Spain. 

Ships  with  yellow  fever  on  board  have  occasionally  arrived  at  English  and  French 
ports,  but  local  conditions  have  apparently  not  been  favorable  to  an  extension  of  the 
disease,  except  to  a  limited  extent  at  Brest,  in  1856,  at  St.  Nazaire,  in  1861,  and  at 
Swansea  (Wales),  iu  1864. 

BAHAMA  ISLANDS. 

Bahama  Islands. — Yellow  fever  prevailed  as  an  epidemic  at  Nassau  in  1861,  1862, 
1863,  and  in  1869. 

According  to  Hirsch  yellow  fever  prevailed,  to  a  limited  extent,  at  Halifax  (latitude 
iA9  26)  in  1861,  and  at  Quebec  (latitude  46-  50')  in  1805. 


ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER.      43 


PREVALENCE  OF  YELLOW  FEVER  IN  THE  UNITED  STATES. 

New  HamjysMre. — Portsmouth  is  tlie  most  uortbern  i)oi:it  in  the  United  States  wliich 
has  suffered  an  epidemic  of  yellow  fever.  In  1798,  and  again  in  1802,  during  which 
year  the  disease  was  epidemic  in  New  York  aud  iu  Philadelphia,  it  was  also  epidemic 
in  this  city. 

Massachusetts. — In  1693  an  English  expedition  sailed  from  Boston  for  the  purpose 
of  taking  from  the  French  the  Island  of  Martinique.  The  expedition  failed  in  its 
object  aud  returned  to  Boston  on  June  17  with  yellow  fever  on  board  the  vessels 
of  the  fleet.  Hutchinson,  in  his  "  History  of  Massachusetts  Bay,"  says  the  mortality 
among  the  sailors  had  been  1,300  out  of  a  total  strength  of  2,100,  and  that  out  of  the 
same  number  of  soldiers  the  loss  was  1,800.  He  states  that  the  disease  spread  from 
the  fleet  to  the  town,  and  that  many  fauulies  left  town  and  resided  in  the  country 
until  the  infection  had  ceased.  This  is  the  first  authentic  account  of  the  occurrence 
of  yellow  fever  within  the  present  limits  of  the  United  States.  In  1796  the  disease 
prevailed  to  a  limited  extent  in  Boston  and  in  Newburyport.  In  1798  it  prevailed  as 
an  epidemic  in  Boston,  where  the  mortality  was  200;  and  iu  1802  60  fatal  cases 
occurred  in  the  same  city.    Some  cases  also  occurred  in  the  years  1800,  1819,  and  1858. 

Ehode  Island. — The  city  of  Providence  was  several  times  visited  by  yellow  fever 
during  the  latter  part  of  the  eighteenth  and  the  beginning  of  the  present  century — 
1794,  1795  (mortality  45),  1797  (mortality  45),  1800,  1805.  The  disease  prevailed  at 
Newport  in  1798,  and  at  Bristol  in  1797. 

Connecticut. — The  disease  prevailed  at  New  London  in  1795,  aud  again  in  1798 
when  the  mortality  was  81.  Hirsch  records  the  occurrence  of  the  disease  at  New 
Haven  in  1743,  1794,  aud  1805;  at  Middletown  in  1820 ;  at  Chatham  in  1796,  and  at 
Hartford  iu  1799. 

New  Yorh. — Epidemics  of  greater  or  less  extent  have  occurred  in  New  York  City 
and  its  immediate  vicinity  in  1693,  1702,  1743  (mortality  217),  1745,  1762,  1791,  1794, 
1795  (mortality  730),  1798  (mortality  2,080),  1799  (mortality  76),  1800,  1801,  1803 
(mortality  700),  1805  (mortality  340),  1809,  1819,  1822  (mortality  230),  1848,  1853, 
1854,  18.56,  1870  (mortality  49). 

Netv  Jersey.— Hirsch  records  the  following  local  epidemics:  Bridgetown,  1798* 
Chews,  1798;  Woodbury,  1798;  Perth  Amboy,  1811. 

Pennsijlvama. — According  to  La  Roche,  "  the  earliest  onset  of  the  disease  occurred 
in  1699,  when  Philadelphia,  then  but  seventeen  years  of  age,  was  little  more  in 
point  of  extent  than  an  ordinary  country  town."  There  are  no  medical  accounts  of 
this  epidemic,  but  there  is  no  doubt  as  to  the  nature  of  the  disease,  which  caused  a 
mortality  of  22p  in  the  new  city,  estimated  to  have  contained  less  than  4,000  inhab- 
itants. The  next  epidemic  in  Philadelphia  occurred  in  1741,  when  the  mortality  was 
250.  Subsequent  epidemics  occurred  in  1747,  1762,  1793  (mortality  4,041),  1794  1797 
(mortality  1,300),  1798  (mortality  3,500),  1799  (mortality  1,000),  1802  (mortality  307), 
1^03  (mortality  195),  1805  (mortality  400),  1819,  1820  (mortality  83),  1853  (mortality 
128),  1870  (mortality  18). 

Delaware.— In  the  epidemic  of  1798  the  city  of  Wilmington  suffered  a  loss  of  250. 

Maryland.— Bp\dem\cs,  for  the  most  part  of  limited  extent,  have  occurred  in  Balti- 
more iu  the  years  1783,  1794,  1797,  1798,  1799,  1800,  1802,  1819,  1820,  1821,  1822,  1868, 
1876. 

Virginia.— At  Norfolk  epidemics  are  recorded  as  follows:  1737,  1741,  1794  1795 
1797,  1799,  1800  (mortality  250),  1801,  1821,  1826,  1855  (mortality  1,807).  An  epi- 
demic occurred  at  Petersburgh  in  1798,  and  at  Alexandria  in  1803.  At  Portsmouth 
the  disease  prevailed  in  1852,  1854,  and  18.55  (mortality  1,000). 

North  Carolina.— Wihmngton,  1796,  1800,  1821,  1«62  (mortality  446) ;  Newbern, 
1799,1864  (mortality  700)  ;  Beaufort,  1854,  1864  (mortality  68),  1871 ;  Washington^ 
1800;  Smithville,  1862. 

South  Carolina. — The  first  epidemic  of  which  we  have  any  account  in  Charleston 


44 


ETIOLOGY    AND    PREVENTION    OP    YELLOW    FEVER. 


occurred  in  1693;  from  tliis  time  epidemics  have  beeu  uninerous,  and  during  the  first 
half  of  the  i)resent  century  the  iihysiciaus  of  Charlestou  gcuerally  considered  the 
disease  endemic  iu  that  city.  That  it  was  not  seems  to  be  demoustrated  by  the  im- 
munity enjoyed  since  1871,  an  immunity  which  is  probably  due  to  the  diminished 
commerce  with  infected  ports  in  the  West  Indies,  and  to  a  more  efficient  quarantine 
service,  since  the  fact  has  been  recognized  that  the  disease  is  not  endemic. 

The  prevalence  of  yellow  fever  in  Charleston  during  the  present  century  is  shown 
in  the  following  table;  recorded  epidemics,  prior  to  the  year  1800,  are  as  follows: 
169;?,  1699,  1700,^  1703,  1728,  1732,  1734,  1739,  1745,  1748,  1753,  1755,  1761,  1762,  1768, 
1770,  1792,  1794,  1795,  1796,  1797,  1798,  1799  (mortality  239).  An  epidemic  occurred 
among  the  troops  stationed  at  Hilton  Head  in  1862  ;  Port  Royal,  1877  (mortality  25). 

Mortality  from  Yellow  Fever  in  CharJesfon,  S.  C;  Pensacola,  Fla.;  Mohile,  Ala.;  Keic  Or- 
leans, La.;  and  Galveston,  Tex.,  during  the  jyresent  century. 


Tear. 

Charles- 
tou. 

Pensa- 
cola. 

Mobile. 

New 
Orleaua, 

G.alves- 
tou. 

Year. 

Charles- 
ton. 

Pensa- 
cola. 

Mobile. 

New 
Otleans. 

G-alvcs- 
tou. 

1800 

184 

(*) 
(*) 
(*) 

1841 
1842 
1843 
1844 
1845 
1840 
1847 
1848 
1849 
1850 
1851 
1852 
1853 
1854 
1855 
1856 
1857 
1858 
1859 
1800 
1861 
1802 
1803 
1864 
1865 
1860 
1807 
1808 
1809 
1870 
1871 
1872 
1873 
1874 
1875 
1870 
1377 
1878 
1879 
1880 

1 
1-J5 

(*) 
(*) 

n 
(■■) 
(*) 
(*) 
C) 

(*) 
GO 
240 
'*) 

70 

75 
50 

594 
211 
487 
148 

160 

2,  259 

850 

737 

102 

10 

415 

7,970 

2,  423 

2,070 

74 

199 

3,889 

1801 

1802 
1803 

90 

(*) 

148 
(*) 

400 

1804 

(*) 

1805 

1800 

200 

1807 

lOJ 

1808 

(*) 

....... 

18L0 

(*) 

1811 
1812 

n 

(*) 

(*) 

310 

027 

n 
n 

115 

536 

1813 

404 

1814 

1815 

211 
13 

717 

1810 

1817 

272 

800 
115 
2,190 
(*) 

(*) 

(*) 

34  4 

1818 

182 

1819 

177 

274 

18''0 

1821 

(*) 
(") 

(*) 

1822 

2 

257 

239 

1 

108 

49 

5 

109 

130 

215 

117 

2 

18 

210 

95 

284 

5 

442 

17 

452 

3 

250 

18 -"3 

259 

1824 

235 
2 

(*) 

1895 

1,150 

1826 

34 

(*) 

3,093 

1827 

04 
20 

(*) 

130 

18''8 

1829 

{*) 

587 
55 
40 

225 

1830 

30 

213 

1831 

1832 

CI 
118 

27 

1833 

18  !4 

49 
25 

CO 

1835 

1830 

1837 

350 

00 

COO 

1838 

?51 
134 
22 

1839 

C-) 

C50 

1840 

(')  Number  of  deaths  uot  stated. 


ETIOLOGY    AND    PEEVENTION    OF    YELLOW    FEVER.  45 

Georgia. — At  Savannah  epidemics  are  recorded  in  the  years  1800,  1807,  1808,  1817, 
1819,  1820,  1827,  1852,  1853,  1854  (mortality  580),  1858,  1876;  at  St.  Mary's  in  1808 
(mortality  84)  and  in  1854 ;  at  Augusta  in  1839  and  1854 ;  at  Bainbridge  in  1873  ;  Bruns- 
wick, 1876. 

Florida. — Tlie  principal  seaport,  Pensacola,  has  suffered  frequent  epidemics  of 
yellow  fever.  Those  occurring  during  the  present  century  are  included  in  the  table 
given  above.  Two  epidemics  are  recorded  as  occurring  prior  to  the  year  1800 — 1764 
and  1765.  At  St.  Augustine  epidemics  occurred  in  1807, 1821, 1838, 1839,  and  1841 ;  at 
Key  West  in  1823, 1829, 1841, 1362, 1867, 1875, 1878, 1887 ;  at  Jacksonville  in  1857, 1877, 
and  1888;  at  Fernandiua  in  1877  (mortality  498) ;    at  Tampa  in  1839, 1853, 1871, 1887. 

Alabama. — The  recorded  epidemics  in  Mobile,  prior  to  the  year  1800,  were  in  1705, 
1765,  and  1766 ;  subsequent  epidemics  are  included  in  the  table.  Montgomery,  1853 
(mortality  35),  1854  (mortality  45),  1855  (mortality  30),  1873  (mortality  102);  Selma, 
1853  (mortality  32) ;  Florence,  1878, 

l/ississijjjji. — The  town  of  Biloxi,  on  the  Gulf,  has  suffered  from  epidemics  as  fol- 
lows: 1702,1839,1847,1853,1858,1878,1884;  Pascagonla,  1847,  1853,  1875,  1878;  Port 
Gibson,  1878;  Shieldsborough,  1820, 1829, 1839  ;  Port  Adams,  1839, 1853 ;  Grand  Gulf, 
1853;  Natchez,  on  the  Mississippi  River,  1817,1819  (mortality  180),  1823  (mortality 
312),  1825  (mortality  150),  1827,1829  (mortality  90),  1837  (mortality  280),  1839  (mor- 
tality 235),1848, 1853, 1855,  1858;  Vicksburg,  1839,  1841,  1847,  18.53,  1855,  1858,  1871, 
1873,1878  (mortality  872);  Jackson,  1853, 1854,  1878  (mortality  86);  Holly  Springs, 
1878  (mortality  309);  Greenville,  1878  (mortality  301);  Grenada,  1878  (mortality 
326) ;  Canton,  1878  (mortality  180).  Our  record  does  not  include  uumerous  smaller 
places  which  suffered  during  the  epidemic  of  1878. 

Louisiana. — The  first  recorded  epidemic  in  New  Orleans  was  in  the  year  1769  ;  other 
outbreaks  prior  to  the  present  century  were  in  1791, 1793, 1794, 1795, 1796, 1797, 1799. 
The  prevalence  of  the  disease  in  this  city  subsequent  to  the  year  1800  is  given  in  the 
table.  Baton  Rouge,  1817, 1819, 1822, 1827, 1829, 1837, 1843, 1847, 1853, 1858, 1878  (mor- 
tality 193);  Opelousas,  1837,1839,1842,  1853  ;  St.  Francisville,  1811,  1817,  1819,  1823, 
1827,1829,  1839,  1843,  1846,  1848,  1853;  Shreveport,  1853,1873  (mortality,  759) ;  Port 
Hudson,  1839, 1841, 1843, 1853, 1878  ;  Thibodeaux,  1846, 1853, 1854, 1878 ;  Washington, 
1837,  1839,  1853,  1854,  1867;  Morgan  City,  1878  (mortality  109).  Numerous  smaller 
places  during  the  epidemics  of  1873  and  of  1878. 

Texas.— The  epidemics  at  Galveston  are  included  in  our  table.  Houston,  1839,  1814, 
1847,  1848,  1853,  1854,  1858,  1859,  1864,  1867,  1870 ;  Huntsville,  1867  (mortality  130); 
Hempstead,  1867  (mortality  151);  ludianola,  1852,  1853,  1858,  1859,  1862,  1867  (mor- 
tality 80);  La  Grange,  1867,  (mortality  200);  Matagorda,  1862  (mortality  120);  Nava- 
zota,  1867  (mortality  154);  Rio  Grande  City,  1867  (mortality  150);  Victoria,  1867  (mor- 
tality 200);  Brenham,  1867  (mortality  120);  Calvert,  1867  (mortality  250);  Chapel 
Hill,  1867  (mortality  123);  Columbia,  1867  (mortality  132);  Brownsville,  1853,  1858, 
1862,  1882. 

Teio/essec— Memphis,  1828,  1853,  1855,  1867,1873  (mortality  1,244),  1878  (mortality 
5,000),  1879  (mortality  485);  Chattanooga,  1878  (mortality  135);  Brownsville,  1878 
(mortality  212);  numerous  smaller  towns  in  1878. 

Arkansas. — Columbia,  1853;  Fort  Smith,  1823;  Little  Rock,  1873;  Napoleon,  1853. 

Kentucky. — Bowling  Green,  1878;  Hickman,  1878  (mortality  153);  Louisville,  1878 
(mortality  64), 

0/iio.— Cincinnati,  1871,  1873,  1878  (mortality  17);  Gallipolis.  1796,  1878  (mortality 
18). 

Illinois.— C-Aixo,  1873  (mortality  17),  1878  (mortality  51). 

Missouri. — St.  Louis,  1854,  1855,  1878  (mortality  16);  New  Design,  1797  (mortality 
57). 

GREAT  EPIDEMICS   IN  THE   UNITED   STATES. 

1793. — The  city  of  Philadelphia,  after  enjoying  an  immunity  from  yellow  fever  for 
31  years,  suffered  in  1793  a  devastating  epidemic.  This  epidemic,  no  doubt,  resulted 
from  importation,  although  a  clear  history  of  its  introduction  was  not  made  out  at 


46  ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER. 

the  time,  and  the  leading  physicians  of  the  city  were  incllued  to  attribute  it  to  local 
origin,  as  a  result  of  unsanitary  conditions  in  connection  with  an  timisually  liigh 
temperature.  LaEocbe  saj'^s:  "Dr.  Eush  and  others  laid  great  stress  on  a  quantity 
of  damaged  coffee  which  was  exposed  during  the  latter  part  of  July,  in  a  place  (on  a 
wharf  and  in  the  adjoining  dock)  and  under  circumstances  wliich  favored  decompo- 
sition. Its  smell  was  highly  putrid  and  offensive,  insomuch  that  the  inhabitants  of 
the  houses  in  Water  and  Front  streets,  who  were  near  to  it,  were  obliged  in  the  hot- 
test weather  to  exclude  it  by  shutting  the  doors  and  windows.  Even  persons  who 
only  walked  along  those  streets  complained  of  intolerable  fetor,  which,  upon  inquiry, 
was  constantly  traced  to  the  putrid  coffee." 

It  appears  jirobable  that  this  -'i^utrid  coffee"  was  indeed  the  nidus  in  which  the 
deadly  exotic  germ  first  developed  which  gave  rise  to  this  fatal  epidemic.  Whether 
the  coffee  was  infected  at  the  port  of  shipment,  or  whether  it  was  transported  in  an 
infected  vessel,  we  can  not  now  determine ;  but  that  the  outbreak  of  yellow  fever  in 
Philadelphia  was  due  to  the  fact  that  the  coffee  was  imported  from  a  region  where 
yellow  fever  was  prevailing,  or  in  an  infected  ship,  rather  than  to  the  fact  that  it 
was  putrid,  can  not  be  doubted,  in  view  of  the  subsequent  history  of  yellow  fever 
epidemics  in  the  United  States. 

As  usual,  the  early  cases  were  not  recognized  as  yellow  fever.  Dr.  Rush  says: 
"The  report  of  a  malignant  and  fatal  fever  being  in  town  spread  in  every  direction, 
but  it  did  not  gain  universal  credit.  Some  of  those  jihysicians  who  had  not  seen 
patients  in  it  denied  that  any  such  fever  existed,  and  asserted  (though  its  mortality 
was  not  denied)  that  it  was  nothing  but  the  common  annual  remittent  of  the  city. 
Many  of  the  citizens  joined  the  physicians  in  endeavoring  to  discredit  the  account  I 
had  given  of  this  fever,  and,  for  a  while,  it  was  treated  with  ridicule  or  contempt. 
Indignation  in  some  instances  was  exerted  against  me."  History  has  repeated  itself, 
in  this  particular,  many  times  in  subsequent  epidemics.  The  early  cases,  even  in 
cities  like  New  Orleans,  where  the  physicians  are  well  acquainted  with  the  disease, 
are  frequently  called  by  some  other  name— '•'bilious  fever,"  "pernicious  fever," 
"  malarial  fever,"  etc. — and  the  physician  who  first  ventures  to  name  the  prevailing 
disease  "yellow  fever"  is  treated  with  ridicule  or  with  indignation. 

It  was  not  until  the  middle  of  August  that  a  rapid  succession  of  fatal  cases  con- 
vinced the  physicians  of  the  city  that  the  fatal  West  Indian  pestilence  was  again 
present  in  Philadelphia. 

The  presence  of  the  disease  was  officially  recognized  on  the  22d  of  August,  when 
the  mayor  of  the  city  gave  orders  for  the  cleaning  of  the  streets  and  general  puri- 
fication of  the  city.  The  disease  continued  to  extend  until  early  in  October,  when 
it  reached  its  height.  It  did  not  cease  entirely  until  abont  the  8th  of  November. 
During  this  short  season  of  prevalence  it  caused  an  enormous  mortality,  distributed 
as  follows:  "August,  325;  September,  1,442;  October,  1,976;  November,  118."  (La 
Roche). 

The  population  of  the  city  at  this  time  is  estimated  to  have  been  a  little  more  than 
40,000,  which  gives  a  mortality  of  10  per  cent,  of  the  total  population  (total  mor- 
tality 4,040).  As  more  than  12,000  of  the  inhabitants  fled  from  the  city,  the  propor- 
tion of  those  who  were  attacked  is  very  great.  La  Roche  estimates  the  total  num- 
ber of  cases  at  11,000. 

1797. — The  ej)idemic  of  this  year  in  the  city  of  Philadelphia  was  less  extended  and 
less  fatal.  The  Avhole  number  of  deaths  is  estimated  to  have  been  about  1,300.  The 
disease,  as  usual,  commenced  in  the  vicinity  of  the  Avharves  (about  the  end  of  July). 
Unsanitary  conditions,  described  by  physicians  who  were  witnesses  of  the  epidemic, 
furnished  the  favorable  local  nidus  for  the  exotic  germ,  which,  according  to  a  report 
of  the  College  of  Physicians  of  Philadelphia  made  in  response  to  a  request  from  the 
governor,  was  imported  by  two  vessels,  one  from  Havana  and  the  other  from  Port  au 
Prince.  In  this  report  the  College  of  Physicians,  contrary  to  the  prevailing  popular 
opinion,  and  that  of  many  prominent  physicians,  took  the  ground  that  the  unsanitary 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  47 

local  conditions  were  simply  secondary-  or  accessory  causes,  and  recommended  "  a 
more  stringent  system  of  quarantine  regulations,  as  the  most  eftectual  means  of  pre- 
venting the  recurrence  of  the  disease"  (_La  Eoche). 

1798. — The  epidemic  of  1797  was  followed  the  next  year  hy  a  still  greater  one, which 
was  not  confined  to  the  city  of  Philadelphia  alone.  The  disease  prevailed  also  in 
Boston  (mortality  200),  in  Portsmouth,  N.  H.  (mortality  100),  in  Newport,  R.  I.  (mor- 
tality^ 2),  in  New  London,  Conn,  (mortality  SI),  iu  New  York  (mortality  2,0d0),  in 
"Wilmington,  Del.  (mortality  250),  audiu  Charleston,  S.  C.  The  mortality  in  Phila- 
delphia was  3,64.5,  distributed  as  follows:  August,  626;  September,  2,004;  October, 
9i;j;  November  (from  the  1st  to  the  .5th),  72.  The  mortality,  iu  proportion  to  the 
number  of  cases,  in  the  city  of  Philadelphia  was  enormous,  being,  according  to  La 
Roche,  about  as  1  to  1.27  of  those  attacked,  or  nearly  yO  per  cent.  This  is  accounted 
for  partly  by  the  fact  that  the  better  class  of  the  community  left  the  city  as  soon 
as  possible  after  the  outbreak  of  the  disease,  and  the  cases  which  occurred  were  con- 
sequently among  the  poorer  classes,  who  inhabited  the  worst  portions  of  the  city. 
The  prevailing  ideas  as  to  the  treatment  of  fevers  by  depleting  measures,  were 
doubtless  responsible  to  some  extent  for  the  excessive  mortality.  "The  College  of 
Physicians,  faithful  to  the  theory  so  long  entertained  hy  it  in  relation  to  the  cause 
of  the  disease,  assigned  to  the  epidemic  this  year,  as  it  had  done  to  those  of  preceding 
seasons,  a  foreign  origin"  (La  Roche). 

l'!>02. — An  epidemic  of  smaller  proportions  prevailed  in  the  year  1802,  causing  a  mor- 
tality in  Boston  of  60,  in  Philadelphia  of  307,  in  Wilmington  of  86,  in  Charleston  of 
yil.  The  disease  also  prevailed  "extensively"  iu  Baltimore,  hut  no  record  of  mor- 
tiility  is  given.  The  prevalence  of  the  disease  at  the  seaports  mentioned,  especially 
before  the  time  of  railroad  communication,  is  not  to  he  ascribed  to  an  extension  from 
one  to  the  others,  or  to  "  an  epidemic  coustitutiou  of  the  atmosphere  ;  "  but  it  doubt- 
less occurred,  for  the  most  part,  as  a  result  of  independent  importation  from  the  usual 
source  of  the  disease,  the  West  Indies.  Thus  we  find  that  iu  1802,  while  Boston  and 
Philadelphia  suffered  epidemics,  New  York,  lying  between  the  two  infected  points, 
was  free  from  the  disease  (two  cases  only  are  reported). 

18.53. — Passing  over  the  minor  epidemics,  for  the  most  part  limited  to  a  single  city, 
or,  by  coiucidence  merely,  to  two  or  more  distant  sea-ports,  we  come  to  the  epidemic 
of  1853,  which  extended  through  portions  of  the  States  of  Florida,  Alabama,  Louisi- 
ana, Mississippi,  Arkansas,  aud  Texas.  The  towns  which  suffered  in  Florida  were 
Pensacola,  Milton,  and  Tampa.  In  Alabama:  Mobile  (mortality  115),  Cahawba,  Cit- 
ronelle,  Demoj)olis,  Fulton,  Hollywood,  Montgomery  (mortality  35),  Selma  (mortal- 
ity 32),  were  the  principal  towns  visited  hy  the  scourge.  In  Louisiana  the  disease 
prevailed  at  New  Orleans,  with  a  mortality  of  7,970 ;  at  Alexandria,  Algiers,  Bay  St. 
Louis,  Bayou  Sara,  Centreville,  Clinton,  Coultierville,  Franklin,  Opelousas,  Patter- 
sonville,  Plaquemiue,  Shreveport,  Thibodeaux,  Trenton,  Washington,  and  various 
smaller  j»laces.  In  Mississippi:  Biloxi,  Brandon,  Clinton,  Grand  Gulf,  Greenwood, 
Jackson,  Natchez,  Pascagoula,  Pass  Christian,  Port  Gibson,  Washington,  Woodville, 
Yazoo.  In  Arkansas:  Columbia,  Grand  Lake,  Napoleon.  In  Texas:  Brownsville, 
Cypress  City,  Galveston,  Hockley,  Houston,  Indiauola,  Liverpool,  Richmond,  Saluria. 

1867. — The  epidemic  of  this  year  was  widely  extended  in  the  State  of  Texas.  The 
first  recognized  case  iu  New  Orleans  occurred  on  the  10th  of  June.  The  total  mortal- 
ity iu  this  city  was  3,093.  Other  towns  visited  in  Louisiana  were  New  Iberia  and 
Opelousas.  In  Texas  the  first  cases  occurred  at  Galveston  on  the  26th  of  June,  aud 
the  total  mortality  in  this  city  was  1,1.50.  Other  places  visited  by  the  epidemic  were 
Alleyton,  Anderson,  Austin,  Bastrop,  Brenham,  Calvert  (mortality  250),  Chapel  Hill 
(mortality  123),  Corpus  Christi,  Danville,  Goliad,  Hempstead  (mortality  151),  Hunts- 
ville  (mortality  130).  Independence,  Indianola  (mortality  dO),  La  Grange  (mortality 
200),  Liberty,  Millicau.Xavazota  (mortality  154),  Oldtown,  Port  Lavacca,  Rio  Grande 
City  (mortality  1.50),  Victory  (mortality  200). 

1873. — Florida,  Alabama,  Mississippi,  Louisiana,  and  Texas  again  suffered  from  an 
epidemic  of  ^-ellow  fever  in  the  year  1873.     At  Pensacola,  Fla.,  the  first  recorded 


48  ETIOLOGY    A.ND    PREVENTION    OF    YELLOW    FEVER. 

case  occurred  Angust  6,  aud  the  total  mortality  was  61.  In  Alabama  the  disease 
appeared  at  Mobile  on  the  "Slst  of  August,  and  the  total  mortality  was  but  27  ; 
Montgomery  suffered  a  loss  of  102.  In  Louisiana  fhe  mortality  in  the  city  of  New 
Orleans  was  only  225,  although  the  epidemic  had  its  origin  in  this  city.  It  was 
imported  by  the  Spanish  bark  Valparaiso,  which  sailed  from  Havana  June  15  in  bal- 
last, arrived  at  New  Orleans  quarantine  station  June  24,  was  detained  2  days,  and 
came  to  the  citj'-  June  26.  The  first  case  was  the  mate  of  this  vessel,  who  was  taken 
sick  on  board  July  4,  while  she  was  lying  at  the  wharf.  But  for  the  sickness  aud 
death  of  the  mate  of  the  Valparaiso  the  origin  of  this  epidemic  would  have  re- 
mained obscure,  and  the  believers  in  the  local  origin  of  the  disease  would  have  had 
a  strong  case,  for  no  other  cases  of  the  disease  occurred  on  the  Valparaiso.  This  is 
explained  by  the  fact  that  the  crew  consisted  of  acclimated  Spaniards,  and  the  mate 
seems  to  have  been  the  only  susceptible  person  on  board  who  could  serve  as  a  test 
of  the  infection  of  the  vessel  at  her  port  of  departure.  From  New  Orleans  the 
disease  was  carried  to  Memphis  by  the  river  steamer  Bee.  It  caused  a  mortality  in 
this  city  of  2,000.  River  steamers  from  New  Orleans  also  carried  the  disease  to  Shreve- 
port,  La.,  where  the  mortality  was  759.  From  Shreveport  a  refugee  fled  to  the  town 
of  Calvert,  Tex.,  where  he  was  taken  sick  and  died.  An  epidemic  followed  with  a 
total  mortality  of  125.  The  disease  was  also  introduced  by  refugees  to  the  town  of 
Marshall,  Tex.,  where  36  deaths  occurred.  The  epidemic  of  this  year  at  Peusacola, 
Fla.,  was  due  to  an  independent  importation  by  the  ship  Golden  Dream,  and  Mont- 
gomery, Ala.,  became  infecfed  through  refugees  from  Pensacola. 

1378. — The  last  and  most  extended  epidemic  of  yellow  fever  in  the  United  States 
is  that  of  1878,  which  invaded  132  towns  aud  caused  a  mortality  of  15,934  out  of  a 
total  number  of  cases  exceeding  74,000. 

The  origin  of  this  epidemic  was  traced  by  the  president  of  the  Louisiana  State  Board 
of  Health  (Chopin)  to  the  steamer  Emily  B.  Souder,  which  arrived  from  Havana,  May 
23,  and  was  moored  at  the  foot  of  Calliope  street,  New  Orleans.  Dr.  Chopin  says: 
"The  first  cases  of  yellow  fever  in  New  Orleans  in  1878  were  undoubtedly  two  of 
the  officers  of  the  above  steamship,  namely,  Clarke,  the  purser,  and  Elliott,  one  of 
the  engineers."  Infected  centers  were  developed  in  the  vicinity  of  the  houses  in 
which  these  men  were  .sick,  but  not  until  after  an  interval  of  several  weeks,  during 
which,  probably  owing  to  unfavorable  conditions  as  to  temperature,  the  "germs" 
remained  dormant,  or  at  least  multiplied  so  slovvly  as  not  to  cause  an  outbreak  of 
the  disease. 

Fortunately  this  great  eijidemic  has  been  carefully  studied  by  a  "board  of  ex- 
perts, authorized  by  Congress,"  and  we  have  a  very  complete  history  of  its  geograph- 
ical extension,  and  of  the  deadly  results  which  marked  its  course.  The  following 
data  are  from  the  report  of  this  "  board  of  experts." 

Louisiana. — New  Orleans  mortality,  4,600;  AUamands  Station,  17;  Baton  Rouge, 
193;  Bayou  Cypre,  7;  Berwick  City,  7;  Buras  Settlement,  3;  Clinton,  15;  Delhi,  34; 
Delta,  47;  Doualdsonville,  71;  Gretna,  .53;  Hammond,  5;  Henderson,  18;  Houma,  6; 
Jesuits  Bend,  2;  Labadieville,  24;  La  Fourche,  26 ;  Lagouda  and  other  plantations, 
42;  Morgan  City,  100;  Napoleonville,  8;  Paincourtville,  15;  Pattersonville,  47;  Pilot 
Town,  17;  Plaquemine,  125;  Ponchatoula,  3;  Port  Eads,  13;  Port  Hudson,  11;  St. 
Bernard  Parish,  7;  Tangipahoa,  50  ;  Thibodeaux,  65;  Teche  country  plantations,  81. 

Tennessee. — Bartlett,  9;  Brownsville,  212;  Chattanooga,  135 ;  Colliersville,  56;  Ger- 
mantown,  35;  Grand  Junction,  74  ;  La  Grange,  37;  Martin,  40 ;  Mason,  24;  Memphis, 
5,000;  Milan,  12;  Moscow,  35;  Nashville,  6  (all  imported  cases) ;  Paris  and  suburbs, 
23;  Somerville,  57;  White  Station,  50;  Williston,  11. 

^?a&«)Ha.— Decatur,  44;  Floi-ence,  50 ;  ^Huntsville,  12;  Leightoii,  1;  Mobile,  90; 
Stevenson,  6;  Town  Creek,  4;  Tuscaloosa,  2  ;,Tuscumbia,  31. 

ifississippi.— Bay  St.  Louis,  82;  Benton,!;  Biloxi,  45;  Bolton,  34;  Bovina,  7; 
Brown's  plantations,  4;  Canton,  180;  Vicinity  of  Canton,  47;  Dry  Grove,  41;  Friar's 
Point,  7  ;  Gainsville,  2;  Goodrich  Landing,  12;  Greenville,  301 ;  Grenada  and  vicinity, 
343;  Horn  Lake,  2;  Handsborough,  16;  Hernando,  80;  Holly  Springs,  309;  luka,  3; 


ETIOLOGY    AND    PEEVENTION    OF    YELLOW    FEVER.  49 

Jackson,  86;  Lake,  86 ;  Lebanou,  10 ;  Liviugston,  10;  McCouib  City,  21;  Meridian, 
91;  Mississippi  City,  15;  Ocean  Springs,  30;  Osyka,  45;  Pass  Cliristiau,  23;  Pearling- 
ton,  24;  Port  Gibson,  115;  country  about  Port  Gibson,  150 ;  Eefuge  Landing,  11; 
Kocky  Springs,  38;  Scranton,  20 ;  Stoneville,  15  ;  Spring  Hill,  6;  Sulphur  Springs,  5 ; 
Senatobia,  7;  Terrene,  4;  Vicksburg,  872;  vicinity  of  Vicksburg,  300;  Water  Valley, 
64  ;  Winona,  3;  Wintervillo  and  vicinity,  26;  Yazoo  City,  9. 

Kentucky. — Bowling  Green,  19;  Hickman,  153;  Louisville,  61  (mostly  refugees). 

Ohio. — Cincinnati,  17  (refugees) ;  Gallipolis,  18. 

Illinois. — Cairo,  51. 

Missouri. — St.  Louis,  16 ;  quarantine  (near  St.  Louis),  42. 

ETIOLOGY. 

The  preceding  historical  record  shows  that  in  the  United  States,  as  elsewhere,  yel- 
low fever  has  prevailed  more  frequently  in  seaports  than  in  inland  towns,  and  that, 
when  epidemics  prevail  in  the  interior,  their  origin  can  commonly  be  traced  to  the 
nearest  seaport,  or  to  intermediate  towns  in  commuuicatiou  with  it.  Towns  upon 
or  near  the  coast  which  have  no  commerce  are  no  more  subject  to  invasion  by  yellow 
fever  than  are  interior  towns,  unless  it  be  by  reason  of  their  proximity  to  a  seaport. 
Moreover,  the  frequency  of  epidemics  in  oar  southern  seaports,  before  the  era  of  effi- 
cient quarantine  administration,  bears  a  direct  ratio  to  their  commercial  importance 
and  especially  to  their  commercial  intercourse  with  Havana  or  other  endemic  foci  of 
the  disease.  Thus  New  Orleans  suffered  epidemics  of  greater  or  less  magnitude  in 
4doutof  tue  first  60  years  of  the  present  century.  During  the  same  period  (1800-l.-?60) 
Charleston  sufi'ered  28  epidemics;  Mobile,  22;  Pensacola,  17;  Savannah,  9;  Galves- 
ton, 7.  That  local  conditions  are  favorable  for  the  development  of  an  epidemic  at 
many  of  our  interior  towns,  especially  those  located  on  great  rivers  near  the  sea 
level  in  the  Southern  States,  is  amply  proved  by  the  epidemic  of  1378.  That  yellow 
fever  does  not  occur  at  these  towns,  excej)t  as  a  result  of  the  introduction  of  infected 
persons  or  articles,  is  beyond  question.  So,  too.  In  seaport  cities  there  is  no  reason 
for  believing  that  any  radical  change  has  occurred  in  local  conditions  during  the  past 
28  years ;  yet,  during  this  time  New  Orleans  has  only  suffered  6  epidemics,  -while 
during  a  corresponding  period  (28  years)  prior  to  1860  there  were  22  years  of  epi- 
demic prevalence  of  the  disease.  A  similar  comparison  for  Charleston  shows  14 
years  of  epidemic  prevalence  prior  to  1860,  and  only  one  since. 

Up  to  the  year  1860  there  were  many  advocates  of  the  local  origin  of  the  disease  in 
these  seaports,  and  the  disease  was  considered  endemic  by  many  physicians,  both  in 
Cliarleston  and  in  New  Orleans.  But  to-day  scarcely  any  one  questions  the  fact  that 
the  disease,  notwithstanding  its  frequent  prevalence,  was  due  to  importation,  and 
that  it  is  nowhere  endemic  within  the  boundaries  of  the  United  States.  It  is  not 
improbable,  however,  that  in  certain  instances  the  "germs"  of  the  disease  have  sur- 
vived the  winter  season,  and  that  "  sporadic  cases"  and  epidemics  have  occurred  as 
a  result  of  importation  dating  back  one  or  more  years.  It  is  claimed  that  the  epi- 
demic of  1879,  in  the  city  of  Memphis,  was  not  due  to  a  new  importation,  but  re- 
sulted from  the  hibernation  of  germs  in  houses  infected  in  1878.  Dr.  Thornton, 
President  of  the  Memphis  Board  of  Health  during  these  epidemics,  says  :  "  The  dis- 
ease appeared  in  houses  in  tlie  suburbs,  which  were  infected  last  year;"  and  states 
further  that  the  first  case  reported  to  the  health  office  occurred  on  the  8th  of  July, 
at  which  date  the  disease  was  not  prevailing  in  any  part  of  the  United  States.  In 
New  Orleans,  in  epidemic  years,  cases  have  sometimes  continned  to  occur  during  the 
greater  part  of  the  month  of  December,  and  in  Tampa  and  Plant  City,  Fla.,  where 
yellow  fever  was  epidemic  in  the  summer  of  1837,  cases  are  said  to  have  occurred  at 
intervals  throughout  the  winter.  Admitting,  then,  the  probability  that  the  recurrence 
of  the  disease  in  our  Southern  seaports  has  sometimes  been  due  to  the  preservation 
of  infectious  material  in  an  active  state  throughout  the  winter,  we  must  insist,  never- 

4067 4 


50      ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

theless,  that  there  is  uo  satisfactory  evidence  of  the  de  novo  origin  of  f.he  disease  from 
local  causes,  either  in  our  own  country  or  elsewhere  ;  and  that,  wherever  its  original 
liabitat  may  have  been,  the  prevalence  of  the  disease  within  the  period  to  which  our 
authentic  historical  records  relate  has  been  due  to  the  importation  of  cases,  or  of  in- 
fected material,  from  a  previously  infected  place.  In  other  words,  the  disease  is  due 
to  a  specific  infectious  agent. 

As  to  the  nature  of  the  spedjlc  came  of  tlie  disease  there  can  scarcely  be  two  opin- 
ions. The  ijresent  state  of  scie'ice  justifies  the  belief  that  it  is  a  living  microorgan- 
ism;  and  facts  relating  to  the  origin  and  extension  of  epidemics  show  that,  as  in 
chiolera  and  in  typhoid  fever,  tliis  microorganism  is  capable  of  development  outside 
of  the  human  body  nnder  favorable  conditions  which,  will  bo  discussed  hereafter. 
Unfortunately,  the  present  state  of  science  does  not  enable  us  to  give  an  accounb  of 
the  deadly  microbe  which  we  assume  to  be  the  cause  of  the  disease  under  considera- 
tion. We  know  to-day  the  morphological  and  physiological  characters  and  the  hab- 
itat within  the  body  of  an  infected  individual  of  the  specfic  cause  of  cholera,  of 
typhoid  fever,  and  of  relapsing  fever,  but  the  researches  made  up  to  the  present  time 
liave  failed  to  demonstrate  the  "  germ"  of  yellow  fever. 


SUSCEPTIBILITY. 

Individuals  of  every  race  and  of  all  ages,  who  are  exposed  to  the  yellow-fever 
poison  for  the  first  time  during  the  epidemic  x)revalence  of  the  disease,  are  subject  to 
be  attacked.  But  there  is  a  wide  dilference  in  the  degree  of  this  susceptibility  among 
races,  and  among  individuals  of  tbe  same  race. 


It  has  been  asserted  that  the  negro  race  has  a  congenital  immunity  from  yellow 
fever,  but  this  is  a  mistake.  The  susceptibility  of  the  negro  is,  however,  much  less 
than  that  of  the  white  race,  and  among  those  attacked  the  mortality,  as  a  rule,  is 
small.  This  is  shown  by  the  statistics  relating  to  white  and  black  troops  in  the  Brit- 
ish service  at  West  India  stations.  "While  in  Jamaica  the  annual  loss  among  the 
former  amounts  to  102  per  1,000  of  the  mean  strength,  the  deaths  among  the  black  did 
not  exceed  8  per  1,000.  In  the  Bahamas  the  mortality  of  the  whites  was  59  in  1.000, 
that  of  the  blacks,  5.6  in  1,000"  (La  Roche). 

In  the  report  of  the  board  of  experts  appointed  by  Congress  to  investigate  the  epi- 
demicsof  1878,  we  find  the  following  remarks  :  "  Berwick  City,  40  cases  among  colored, 
no  deaths.  Morgan  City,  21  cases  among  colored  persons,  Brownsville,  Tenn.,  of  1(32 
colored  cases  21  died.  Chattanooga,  of  685  casein  256  whites,  429  colored;  of  164 
deaths,  118  whites,  46  colored.  Decatur,  Ala.,  of  64  white  cases  28  died,  of  168  col- 
ored 21  died." 

The  indigeneous  races  of  the  West  Indies  and  of  the  continents  of  North  and  South 
America  have  no  immunity,-  except  suck  as  is  acquired  by  residence  in  an  endemic 
/ocus  of  the  disease,  and  the  same  is  true  of  the  Mongolian  race;  but  like  the  ne- 
gro they  have,  although  to  a  less  degree,  less  susceptibility  than  the  white  race,  and 
the  mortality  among  those  attacked  is  not  so  great. 

In  general,  it  may  be  stated  that  the  natives  of  northern  latitudes  are  more  suscep- 
tible than  those  born  in  tropical  or  subtropical  climates.  Blair,  who  had  an  extended 
experience  in  Guiana,  says  :  "  The  lower  the  winter  temperature  in  the  native  country 
of  those  attacked  the  more  severe  was  their  sickness,  so  that  while  the  mortality 
among  West  Indians  amouuted  to  only  6.9  per  cent,  of  the  sick,  it  rose  to  17.1  among 
the  Italians  and  French,  19.3  among  the  English, 20. 2  among  the  Germans  and  Dutch, 
and  27.7  among  Scandinavians  and  Russians." 

Barton  gives  the  following  figures,  showing  the  mortality  per  thousand  among 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  51 

dififereut  races,  aud  those  of  the  same  race  from  different  latitudes,  in  the  city  of 

New  Orleans  in  the  great  eijideinic  of  1»53 : 

Per  1,000. 

Native  Creoles •. 3.  58 

Strangers  from — 

AVest  Indies.  Mexico,  and  South  America 6. 14 

Southern  States  of  the  Union 13. 22 

Spain  and  Italy 22.06 

Middle  States  of  the  Union 30.69 

New  York  and  New  England  States 32.83 

Western  States  of  the  Union 44.23 

France 48. 13 

British  America 50.24 

Great  Britain 52. 19 

Germany 132.  01 

Scandinavia 163.  26 

Austria  and  Switzerland 220.  08 

Netherlands 328.94 


There  is  probably  no  difference  in  the  susceptibility  of  the  sexes,  but  males  are  at- 
tacked in  greater  proportion  than  females,  because  they  more  frequently  and  often 
recklessly  visit  infected  localities.  The  n'-ortality  is,  as  a  rule,  considerably  greater 
among  males.  Ligou,  in  giving  an  account  of  the  pestilence  at  Barbadoes  in  1647, 
of  which  he  was  an  eye-witness,  says:  "The  cause  was  unknown;  one  could  not 
say  if  the  ships  of  commerce  had  imported  the  scourge,  or  if  it  came  from  bad.  food, 
marshy  water,  the  intemperance  of  the  colonists,  and,  above  all,  the  great  quantity 
of  eau-de-vie  which  they  drank.  *  *  *  It  was  the  most  debauched  who  perished 
first,  and  not  one  woman  died  for  ten  men."  No  doubt  Ligon  was  right  in  ascribing 
the  difference  in  the  mortality  of  the  sexes  largely  to  the  difference  in  their  habits, 
with  reference  to  the  use  of  eau-de-vie.  Those  who  habitually  use  spirituous  liq- 
uors are  less  likely  to  recover  from  an  attack  than  the  temperate,  and  a  recent  de- 
bauch is  a  recognized  predisposing  cause.  Sailors  who  go  on  shore  at  an  infected 
port  for  "  a  little  spree"  very  commonly  turn  up  in  the  hospital,  or  are  taken  sick 
after  they  come  on  board  ship,  and  serve  as  the  starting  point  of  an  epidemic  among 
their  comrades,  and  subsequently  perhaps  at  the  porb  of  destination  of  the  vessel. 
The  greater  prevalence  and  severity  of  the  disease  in  epidemics  among  males  has 
been  noticed  by  numerous  authors,  and  has  been  verified  in  the  writer's  personal 
experience. 

AGE. 

Infants  and  old  persons  enjoy  a  comparative  immunity,  due  in  part,  no  doubt,  to 
the  fact  that  they  are  less  exposed  than  active  individuals  in  middle  life.  Dr.  Rush 
records  the  fact  that  he  has  "  met  with  a  violent  case  of  the  disease  in  a  child  of  four 
months,  and  a  moderate  case  in  a  child  of  ten  weeks"  (La  Roche).  Very  j^ouno- 
infants,  however,  connnonly  escape,  or  suffer  so  mild  an  attack  that  the  Jiature  of  the 
disease  is  not  recognized.  In  cities  like  New  Orleans,  which  have  suffered  repeated 
epidemics,  the  proportion  of  children  attacked  is  often  exceptionally  large,  because 
they  constitute  a  large  share  of  the  unacclimated  population,  having  been  born  since 
the  last  epidemic.  Dr.  Bemiss  has  given  the  following  table,  showing  the  number 
attacked  and  the  comparative  mortality  for  different  ages,  in  the  great  epidemic  of 
1878. 

The  results  of  private  practice  in  New  Orleans  are  exhibited  in  the  following  sta- 
tistics. Four  of  the  principal  practitioners  in  the  city  treated,  in  private  practice, 
975 patients— 909  white,  and  66  colored.    Of  the  former,  92,  or  10.11  per  cent.,  died; 


52 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVEK. 


of  the  colored  only  2  died.     The  cases  and   deaths   among  the  whites,  classified  by 
age,  are  as  follows  : 


Age. 


Cases.  Deaths.  Percent. 


Under  5  years  of  age 

From  5  to  10  years  of  age . 
From  10  to  20  years  of  age 
From  20  to  iO  years  of  age 
Froiu  40  to  60  years  of  age 
From  60  to  80  years  of  age 


206 

26 

12.67 

233 

20 

8.61 

183 

9 

4.9 

232 

39 

10.7 

47 

6 

12.7 

i 

2 

50.0 

This  table  does  not  support  the  statement  that  adults^are  more  likely  to  be  attacked 
than  children,  but  it  must  be  remembered  that  it  relates  to  cases  occurring  in  private 
practice,  in  a  community  in  which  the  adults  were  largely  protected  by  previous 
attacks,  or  by  passing  through  repeated  epidemics. 

In  a  review  of  the  mortality  in  the  same  epidemic,  with  reference  to  age,  Dr.  C. 
B.  White  arrives  at  the  following  conclusions  : 

"First.  That  the  mortality  of  boys  at  4  years  is  not  because  a  very  much  larger 
number  of  boys   were  taken  sick,  but   that  there   is  an  actual  greater  mortality. 

"Second.  It  is  seen  that,  though  the  deaths  decline  with  great  rapidity — being  at 
4  years  344;  at  5  years,  169;  at  6  years,  65,  the  cases  do  not  decrease  in  the  same  ratio, 
but  decline  at  folio vrs:  Cases  at  4  years  822;  cases  at  5  years,  740;  cases  at  6  years, 
624:  the  recoveries  being  proportionally  much  larger. 

'•Third.  From  7  to  11  years  of  age  the  death  rate  remains  uniform,  the  disease  being 
comparatively  much  less  fatal.  According  to  Dowler,  the  mortality  among  children 
in  the  epidemic  of  Idll,  in  New  Orleans,  was  very  small.  On  the  other  hand,  in  the 
epidemic  of  1853,  in  the  same  city,  it  was  considerable." 

Dr.  Charles  Delery  has  given  the  following  table,  compiled  from  the  official  reports 
in  the  office  of  the  board  of  health,  showing  the  mortality  during  the  epidemic  of 
1:;07,  among  children  born  in  the  city  of  New  Orleans  : 


Below  1  year 

1  to  2  years  - 

2  to  3  years 

3  to  4  years. . 

4  to  5  years  . 

5  to  6  years . . 
0  to  7  years.. 

7  to  8  years.. 

8  to  9  years.. 

Total  - 


Males.     Females.     Total 


139 


9 

18 

18 

40 

23 

41 

10 

29 

9 

22 

10 

2.5 

5 

29 

9 

19 

1 

10 

233 


Total  deaths  from  July  29  to  November  7,  1867  :  Males,  167  ;  females,  133  (of  these 
5  colored,  2  males  and  3  females). 

Dr.  Henry  Smith,  Marine  Hospital  service,  reports  that  in  the  epidemic  at  Shreve- 
port.  La.,  in  1873,  out  of  a  total  of  534  deaths  in  which  the  age  was  ascertained  "100 
died  under  10  years  ot  age,  93  died  between  10  and  20  years  of  age,  156  died  between 
20  and  30  years  of  age,  134  died  between  30  and  40  years  of  age,  59  died  between  40 
and  50  years  of  age,  29  died  between  50  and  60  years  of  age,  13  died  above  60  years 
of  age," 


ETIOLOGY    AND    PEEVENTION    OF    YELLOW    FEYER.  53 

IMMUNITY. 

Immunity  is  acquired  by  suffering  an  attack  of  the  disease,  or  by  long  residence  in 
localities  where  it  is  endemic  or  prevails  frequently  as  an  epidemic;  this  acquired 
immunity  is  not,  however,  absolute. 

Second  attacks  no  doubt  occasionally  occur,  although  this  lias  been  denied  by  some 
authors.  Blair,  whose  experience  was  very  great,  says  that  he  does  not  believe  there 
is  an  instance  of  a  second  attack  after  a  month's  perfect  restoration  to  health.  Other 
authors  are  equally  positive  in  their  statements.  On  the  other  hand,  we  have  numer- 
ous authentic  accounts  of  second  attacks.  Thus  "Dr.  Jackson  states  that  in  Spain, 
daring  the  epidemic  of  1820,  20  well-authenticated  instances  came  within  his  knowl- 
edge of  persons  being  attacked  who  had  had  the  disease  before."  Dr.  VVragg, 
speaking  of  the  epidemic  in  Charleston  in  1854,  reports  the  occurrence  of  second 
attacks  in  a  number  of  instances,  aud  says:  "Six  of  these  were  so  well  proved  as  to 
admit  of  no  douljt  on  the  sulijcct.  Some  of  the  patients  were  identified  as  having 
gone  through  the  fever  in  this  (the  Eoper)  hospital  in  1852,  throwing  up  black  vomit 
on  both  occasions."  (La  Eoche.)  Dr.  Eush  has  given  evidence  of  the  same  kind, 
and  says  that  a  second  attack  was  more  common  when  the  first  had  been  compara- 
tively mild. 

Dr.  Delery,  in  his  account  of  the  epidemic  of  1867  in  the  city  of  New  Orleans, 
gives  3  cases  of  second  attacks,  1  fatal,  in  which  the  first  attack  occurred  in  a 
previous  epidemic  in  the  same  city,  and  was  vouched  for  by  experienced  physicians 
known  to  him.  While,  then,  it  can  not  be  denied  that  second  attacks  occasionally 
occur,  the  evidence  of  experienced  observers  in  all  parts  of  the  yellow  fever  zone  is 
opposed  to  the  view  that  this  is  a  common  occurrence.  Those  who  have  considered 
yellow  fever  nothing  more  than  a  grave  form  of  malarial  fever,  an  idea  which  was 
entertained  by  numerous  jihysicians  in  this  country  and  in  the  West  Indies  in  the 
early  part  of  the  present  ceutnry,  very  naturally  failed  to  differentiate  the  disease 
from  the  endemic  malarial  fevers  which  they  encountered,  and  believed  that  it  might 
recur  an  indefinite  number  of  times. 

ACCI.IMATIZATIOX. 

It  is  a  remarkable  fact  that  the  population  of  a  larce  city  like  Havana,  or  Eio 
Janeiro,  in  which  yellow  fever  has  been  endemic  for  a  series  of  years,  enjoys  such  a 
degree  of  immunity  from  the  effects  of  the  deadly  poison  that  there  is  no  interrup- 
tion of  business  or  pleasure  at  a  time  when  strangers  in  the  city  are  falling  sick  oil 
every  side.  The  development  of  an  epidemic  in  these  cities  depends  upon  the  presence 
of  susceptible  strangers  in  sufficient  number  to  furnish  a  series  of  cases  considered 
large  enough  to  justify  the  use  of  the  word.  The  presence  of  but  few  strangers  dur- 
ing the  epidemic  season  leads  to  the  announcement  that  the  disease  is  not  epidemic, 
but  that  sporadic  cases  occur  from  time  to  time.  Under  exceptional  circumstances, 
however,  epidemics  are  developed  in  these  endemic  foci  of  the  disease,  in  which  those 
who,  by  birth  or  long  residence,  were  supposed  to  be  acclimatized  furnish  a  certain 
quota  to  the  general  mortality.  This  has  frequently  occurred,  for  example,  in  the 
city  of  New  Orleans,  where  yellow  fever  formerly  prevailed  almost  annually,  and 
where  the  create  population  was  supposed  to  enjoy  an  hereditary  immunity.  Dowler, 
who  has  made  a  special  study  of  the  question,  says  of  the  creole  population  of  New 
Orleans  : 

"A  few  physicians  aud  others,  mostly  advocates  of  the  contagiousness  of  yellow 
fever,  maintain  that  all  the  Creoles  of  New  Orleans,  not  less  than  strangers,  have  this 
disease  once  during  life,  for  the  most  part  during  childhood,  and  that  it  proves  fatal 
to  many  of  them." 

"This  sweeping  statement,  however,  is  with  few  exceptions  erroneous,  as  may  be 
proved  by  authentic  documents  concerning  all  of  the  epidemics  witnessed  by  the 
writer  for  17  years,  not  excepting  the  extraordinary  one  of  1853  itself." 

'•  It  will  have  been  remarked  by  careful  observers  that  many  families  have  settled 
in  New  Orleans  for  half  a  lifetime  without  ever  having  had  yellow  fever.    Indeed,  it 


54  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVEK. 

has  beeu  tliougLt  by  many  physicians,  j)reYious  to  1353,  that  at  least  one-third  of  all 
strangers  settling  perniauently  in  New  Orleans  escaped  yellow  fever  altogether." 

"  Tlie  exemption  of  the  creolized  of  the  city  is  a  fact  which  every  epidemic  has 
coufiraied ;  for  example,  take  that  of  1841,  in  which  1,800  died,  fj  of  whom  only  were 
natives  of  the  city,  1  aged  3  weeks ;  3,  2  years.  In  1843,  among  692  deaths  from 
yellow  fever  bnt  2  are  certified  as  having  been  born  in  New  Orleans." 

The  writer  quoted  believes,  with  many  other  physicians  residing  in  endemic  foci 
of  the  disease,  that  immnuity  is,  "  to  a  great  degree,  hereditary,  or  transmissible 
from  parents  to  children."  This  is  generally  accepted  among  the  physicians  and  the 
native  population  of  the  city  of  Havana ;  but  there  is  reason  to  believe  that  it  is  a 
mistake,  and  that  the  Creole  child  owes  his  immunity  not  to  his  parents,  but  to  indi- 
vidual acclimatization,  and  not  infrequently,  to  say  the  least,  to  a  mild,  unrecognized 
attack  of  yellow  fever.  Dr.  Dowler  says  that  "  many  creole  children  had,  during 
the  epidemic  of  1853,  a  fever,  a  slight  fever,  yellow  fever  if  you  please,  known  as 
such  rather  by  the  coexistence  of  the  epidemic  than  from  any  severe  symptoms 
among  these  children,  a  slight  fever  never  yet  described,  having  generally  but  one 
paroxysm,  lasting  from  six  hours  to  one,  two,  or  three  days,  scarcelyever  requiring 
medication.  That  a'  few  of  these  cases  acquired  an  alarming  violence,  and  even 
proved  fatal,  is  most  true,  most  deplorable." 

Hinemann  writes  with  reference  to  Vera  Cruz:  "Until  lately  the  physicians  and 
people  of  Vera  Cruz  supported  with  fanaticism  the  dogma  that  natives  were  abso- 
lutely exempt  from  yellow  fever.  But  the  fearful  epidemics  of  recent  years  (1875, 
1877,  1878)  have  worked  a  change;  for  so  many  native  children  and  adults  suffered 
that  the  truth  could  no  longer  be  denied  that  these  do  not  enjoy  an  absolute  immu- 
nity." 

In  Cuba  the  dogma  that  Creoles  are  exempt  from  yellow  fever  did  not  withstand 
the  searching  investigation  made  by  the  Havana  yellow-fever  commission  of  1879. 
We  quote  some  of  the  evidence  collected  and  reported  by  Dr.  Chailie,  president  of 
this  commission:  "  Dr.  Navea,  of  San  Jose  de  las  Lajas,  an  inland  town  some  20 
miles  southeast  of  Havana,  presented  the  following  interesting  report  after  it  had 
received  the  full  approval  of  Drs.  Cabrera  and  Bofil,  his  colleagues  at  San  Jos6:  *  We 
have  here  annually,  in  the  practice  of  the  three  physicians,  from  twenty  to  thirty 
Cuban  children  and  from  thirty  to  forty  Cuban  adults  attacked  with  bilious  remit- 
tent fever,  which  is  popularly  designated  typhus.  There  is  nothing  whatever  to  con- 
stitute a  differential  diagnosis  between  this  fever  of  the  natives  and  the  yellow  fever 
of  strangers.  It  is  characterized  by  its  hemorrhagic  tendency,  albuminuria,  black 
vomit,  and  all  the  symptoms  of  yellow  fever.  It  is  so  well  marked  that  even  when 
seen  by  the  uneducated  they  exclaim,  "  Vomito!"  The  treatment  for  the  one  is  best 
for  the  other.  We  have  never  seen  a  second  attack  of  this  bilious  remittent  fever, 
nor  one  who  had  recovered  from  it  attacked  with  yellow  fever.  If  any  one  of  us 
three  physicians  here  sees  this  fever  attack  a  native  Cuban  we  say  "bilious  remit- 
tent fever, "  and  if  it  attacks  a  person  not  a  native  of  Cuba  we  say  "yellow  fever ;  " 
but  at  bottom  it  is  the  same  disease,  and  we  agree  to  call  it  bilious  remittent  fever 
in  Cubans  solely  because  these  believe  themselves'  exempt  from  yellow  fever,  and 
are  so  prejudiced  that  they  would  be  alarmed  if  assured  their  disease  was  really 
yellow  fever." 

Dr.  Mantiguazi,  of  Cienfuegos,  reported  as  follows:  "During  December,  1875,  the 
sanitary  condition  improved,  but  a  certain  fever ha=i  prevailed  among  children,  which 
is  known  here  as  typhus,  although  it  resembles  in  nothing  the  disease  to  which  Euro- 
peans give  this  name,  and  which  so  often  occurs  in  camps.  By  this  fever  I  have  lost 
one  patient,  a  child  8  years  of  age,  born  in  this  town.  It  presented  all  the  symptoms 
of  yellow  fever,  for  on  the  second  day  this  patient  had  the  characteristic  vomit  and 
stools,  and  died  on  the  third  day.  In  a  consultation  with  three  other  physicians  they 
agreed  with  me  in  my  diagnosis,  with  this  difference,  that  they  said  that  these  same 
symptoms  which  constituted  yellow  fever  in  strangers  constituted  in  natives  typhus. 
I  have  been  told  that  eight  to  ten  children  have  died  of  this  disease." 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER.  55 

Dr.  Mazarredo,  a  grartnate  of  Paris,  who  had  had  20  years'  experience  in  Cnba, 
wrote  as  follows:  "In  ray  owu  practice  I  have  seen  cases  of  yellow  fever  in  children 
from  1  to  5  j'ears  of  age,  and  even  not  over  a  year  of  age,  in  whom  it  has  been  fatal, 
and  I  am  now  well  convinced  that  children  horn  in  Cienfuegos  are  exactly  in  the  same 
conditions  the  first  years  of  their  lives  as  are  other  newcomers  and  just  as  liable  to 
its  attacks.  Nevertheless  I  consider  that  childrcu  are  generally  less  prone  to  suffer 
severely.  ■•  *  «  Worthy  practitioners  of  this  locality  give  the  name  of  typhus 
fever  to  these  cases,  and  although  they  admit  that  no  difi:erence  whatever  exists  be- 
tween the  symptoms,  march,  and  duration  of  this  compared  with  yellow  fever,  still 
they  think  the  former  a  swamp  fever,  and  hence  more  amenable  to  quinine." 

Blair,  who  has  written  a  classical  account  of  the  epidemic  of  1851-'.54  in  British 
Guiana,  says  that  "infancy  was  one  of  the  most  favoring  causes  of  the  action  of  the 
yellow-fever  poison.  The  constitution  of  tlie  new-born  or  young  white  Creole  was 
highly  susceptible.     He  or  she  was  truly  in  the  category  of  newcomers." 

Recent  experience  at  Key  West  (epidemic  of  1887)  shows  that  the  children  of  accli- 
mated Cubans,  born  since  the  arrival  of  their  parents  at  Key  West,  have  the  same 
susceptibility  to  the  disease  as  other  children  born  of  native  (creole)  parents.  We 
can  not,  therefore,  admit  that  inherited  immunity  has  been  established. 

On  the  other  hand,  we  are  not  prepared  to  assert  that  there  is  no  immunity  inde- 
pendent of  an  attack  of  the  disease.  Unrecognized  mild  attacks  in  adults,  and  espe- 
cially in  the  negro  race  and  among  creole  children,  are  no  doubt  of  frequent  occur- 
rence. But  it  can  not  be  denied  that  independently  of  any  febrile  manifestations 
individuals  of  all  ages  who  have  resided  in  an  infected  locality  for  sometime  acquire 
a  comparative  immunity,  which  increases  with  length  of  residence  and  degree  of  ex- 
posure to  the  action  of  the  specific  cause  of  the  disease. 

It  is  generally  conceded  that  this  acclimatization  is  lost,  or  at  least  reduced  to  a  con- 
siderable extent,  by  residence  for  some  years  in  a  latitude  outside  of  the  "yellow 
fever  zone."  And  some  authors  maintain  that  the  immunity  due  to  an  attack  of  the 
disease  is  in  like  manner  lost  by  a  protracted  absence  from  its  accustomed  haunts. 
The  writer's  observations  are  opposed  to  the  latter  statement.  In  the  epidemic  at 
Fort  Barrancas,  Fla.,  in  1875,  in  which  nearly  every  unprotected  person  who  remained 
in  the  infected  area  suffered  an  attack,  three  officers,  who  had  previously  had  yel- 
low fever,  remained  in  perfect  health,  although  they  had  all  resided  for  several  years 
in  a  northern  locality  since  the  date  of  their  attack — one  for  more  than  20  years. 

Hinemann,  who  has  had  an  extended  experience  at  Vera  Cruz,  Rays  that  "even  for- 
eigners may  remain  insusceptible  to  the  disease  for  a  considerable  number  of  years, 
provided  they  do  not  leave  the  focus  of  the  disease  during  that  period.  An  absence 
of  a  few  months  only  is  sufficient  to  take  away  this  immunity. 

The  fact  that  foreigners  may  remain  for  years  in  Havana,  in  Rio  Janeiro,  or  other 
endemic  foci  of  the  disease  without  suffering  an  attack  is  undeniable,  I  found  this 
especially  to  be  the  case  in  Rio,  where  there  is  a  large  foreign  population.  It  is  true 
that  some  who  have  escaped  for  a  series  of  years  often  fall  sick  at  last  in  a  season  of 
unusual  epidemic  prevalence,  but  comparative  immunity  is  shown  by  the  fact  that, 
as  among  the  creole  x>oi)ulation,  the  disease  is  not  so  fatal  with  them  as  among  newly 
arrived  strangers.  The  efiects  of  acclimatizatioa  in  large  cities,  like  Rio  Janeiro  and 
Havana,  are  illustrated  by  the  fact  that  in  these  cities  yellow  fever  is,  for  the  native 
population,  a  disease  of  minor  importance.    This  is  shown  by  the  following  tables. 

In  Rio,  a  city  having  a  population  of  400,000,  the  mortality  from  some  of  the  prin- 
cipal causes  of  death  is  given  in  the  official  report  of  the  superior  board  of  health,  as 
follows,  for  the  year  18d6,  which  was  considered  an  epidemic  year  so  far  as  yellow 
fever  is  concerned: 

Mortalily. 

1.  Tnljerciilosis 2,  077 

2.  Diseases  of  the  circulatory  apparatus 1,458 

3.  Diseases  of  the  cerebro-spinal  apparatus 1,  345 

4.  Diseases  of  the  digestive  apparatus ],  (197 

5.  Malarial  diseases 1,  OSG 

6.  Yellow  fever ],015 


56  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

In  Havana,  the  principal  causes  of  death  among  the  civil  population,  in  the  year 
1880,  are  given  officially  as  follows: 


1.  Phthisis  pulmonalis 

2.  Diarrhea  ami  enteritis  . 

3.  Yellow  fever 


That  acclimatization  is  not  due  to  the  iniiuence  of  climate,  but  is  an  acquired  tol- 
erance to  the  action  of  the  yellow-fever  poison,  is  shown  by  the  history  of  this  disease 
in  Rio  Janeiro.  At  the  time  of  its  introduction,  in  1&49,  it  found  an  unprotected 
population,  and  for  a  series  of  years  prevailed  as  an  epidemic  among  this  population, 
causing  a  mortality  quite  comparable  to  that  in  similarly  located  cities  in  other  parts 
of  the  world  when  first  invaded  by  the  scourge.  At  present  the  native  population 
furnishes  but  a  comparatively  small  proportion  of  the  total  number  of  deaths  by  this 
disease. 

PREDISPOSING  CAUSES. 

Plethora  is  considere'd  by  many  physicians,  in  the  regions  where  yellow  fever  pre- 
vails, to  be  a  predisposing  cause,  and  to  account  for  the  greater  susceptibility  of 
strangers  from  northern  countries.  Constipation  is  generally  regarded  as  conducive 
to  an  attack.  Other  predisposing  causes  are,  fatigue  from  excessive  exertion,  debility 
resulting  from  a  recent  debauch,  or  from  any  other  cause,  exposure  to  the  direct  rays  of 
the  sun,  violent  inental  emotions,  such  as  grief  ot  fear,  and,  in  general,  any  influence 
capable  of  depressing  the  vital  powers,  or  any  disturbance  of  the  normal  functional 
activities  of  the  body. 

MODE  OF  INFECTION. 

Yellow  fever  is  contracted  by  exposure  in  infected  localities,  and  not  directly  by 
contact  with  the  sick.  This  is  established  by  a  mass  of  evidence  which  is  recorded 
in  the  literature  of  the  subject,  but  is  still  denied  by  some  physicians,  who  regard  it 
as  a  contagious  disease  in  the  same  sense  that  smallpox  and  measles  are  contagious. 
In  this  respect  it  is  like  cholera,  and  typhoid  fever.  There  is  something  given  otf 
from  the  body  of  the  sick  by  which,  when  external  conditions  are  favorable,  new 
centers  of  infection  are  established ;  and  it  seems  probable  that,  as  in  the  diseases 
mentioned,  this  germinal  principle  of  the  disease  is  contained  in  the  alvine  discharges 
of  the  sick.  That  it  is  not  given  off  from  the  general  surface  of  the  body  is  an  infer- 
ence which  we  base  upon  the  es'tablished  fact  that  the  disease  is  not  transmitted 
directly  from  individual  to  individual.  It  is  true  that  the  contagionists  bring  for- 
ward a  class  of  facts  which,  regarded  alone,  seem  to  give  some  support  to  their  views, 
but  we  believe  these  facts  to  be  explicable  in  accordance  with  the  statements  above 
made.  Persons  who  successively  fall  sick  in  the  same  house,  or  on  board  ship,  are 
not  infected  one  from  another,  but  contract  the  disease  from  a  common  source,  the 
infected  premises,  or  ship.  Indirectly,  of  course,  they  contract  the  disease  through 
the  agency  of  the  individual,  or  fomites,  through  whom  the  house  or  ship  first  became 
infected. 

Formerly  the  battle  between  the  contagionists  and  the  noncontagionists  was  one 
involving  the  question  of  local  origin  on  one  side,  together  with  a  strenuous  denial 
of  the  transmissibility  of  the  disease  and  the  value  of  quarantine  restrictions.  The 
contagionists,  on  the  other  hand,  insisted  upon  the  exotic  origin  of  the  disease,  and 
its  transmissibility  by  ships  and  persons.  And  to  this  extent  they  were  right.  There 
can  be  no  doubt  that  the  prevalence  of  the  disease  in  the  United  States  depends  upon 
the  introduction  of  an  exotic  germ  ;  but  it  also  depends  upon  local  conditions  which 
favor  the  development  of  this  germ.  The  yellow  fever  patient,  however  many  germs 
he  may  carry  in  his  intestines  or  elsewhere,  does  not  directly  endanger  those  who 


ETIOLOGY    AND   PREVENTION    OF    YELLOW   FEVER.  57 

come  near  Lim  any  more  than  a  gelatine  stick — culture  of  the  spiiilluni  of  Asia 
cholera,  or  of  the  authrax  bacillus  places  in  danger  the  student  of  l)act»!riology  who 
is  engaged  in  studying  it. 

.  It  is  well  known  to  the  jjeople  of  the  city  of  Mexico  tbat  a  visit  to  the  seacoast  city 
of  Vera  Cruz  daring  the  epidemic  season  is  likely  to  result  in  an  attack  of  yellow 
fever.  It  is  also  well  established  that  those  who  fall  sick  with  the  disease  after  their 
return  to  the  city  of  Mexico  never  communicate  it  to  others  who  are  closely  associ- 
ated with  them  as  attendants,  etc.  The  same  is  true  at  the  health  resort,  Petropolis, 
located  in  the  mountains,  within  a  few  hours'  ride  of  the  city  of  Rio  Janeiro.  Fre- 
quently individuals  fall  sick  at  Petropolis  who  have  visited  the  infected  city  of  Rio. 
Never  do  they  communicate  the  disease  to  others.  This  is  also  the  experience  of  the 
physicians  in  charge  of  hospitals— e.  fj.,  the  Charity  Hospital  of  New  Orleans.  So  long 
as  the  hospital  audits  vicinity  remain  uuiufected,  cases  douotoriginatein  the  hospital, 
although  yellow  fever  patients  may  be  admitted  to  the  wards  with  unacclimatized 
persons  suffering  with  other  diseases,  and  be  cared  for  by  susceptible  attendants. 

In  his  report  upon  the  camps  established  near  Memphis  in  the  epidemics  of  1878 
and  1879,  Colonel  Cameron  makes  the  following  statement :  "  It  was  found  necessary 
that  the  officer  in  authority  should  set  an  example  of  constant  indifference  to  attack 
in  order  to  appease,  as  far  as  possible,  the  constant  anxiety  of  the  population  under 
his  charge.  Especially  was  this  true  in  1878,  as  depopulation  went  on  slowly  that 
year,  and  infected  people  poured  daily  into  the  camps  from  the  more  pestilential  por- 
tions of  the  city.  Very  many  reached  camp  with  the  fever  on  them,  so  that  as  manv 
as  seventeen  persons  fell  victims  in  one  night,  not  a  few  in  their  tents.  In  no  in- 
stance, hoiceDer,  did  they  communicate  the  disease  to  their  families  or  hedfelloivs  as  far  as 
could  be  traced." 

In  the  same  epidemic  (1878)  Dr.  Minor  reports  that  over  thirty  cases  were  discov- 
ered among  refugees  in  Cincinnati,  Ohio,  and  says:  "No  fihysician  or  nurse  con- 
tracted the  disease,  and  in  no  instance  did  it  exhibit  any  tendency  to  spread."  The 
same  was  true  in  Nashville  the  same  year.  Twenty  imi)orted  cases  occurred  in  different 
parts  of  the  city  without  any  local  cases  resulting  from  them  (Report  of  Nashville 
Board  of  Health).  Evidence  of  this  kind  could  be  extended  to  fill  a  volume,  but 
sufficient  has  been  presented  to  establish  the  statement  made,  and  the  reader  may  be 
referred  to  the  "  Proofs  of  Noucontagion,"  in  the  second  volume  of  the  classical  work 
of  La  Roche  (pp.  23C-566). 

We  have  already,  in  discussing  the  nature  of  the  specific  cause  of  the  disease  re- 
ferred to  the  fact  that  there  is  no  satisfactory  evidence  that  the  disease  is  contracted 
by  the  use  of  contaminated  water,  as  is  the  case  in  cholera  and  typhoid  fever.  We 
quote  the  following  conclusions  of  the  board  of  experts  apj)ointed  to  investigate  the 
ejiidemic  of  1878. 

(6)  "  Yellow  fever  is  a  disease  of  singular  local  attachments.  It  often  becomes 
epidemic  in  one  section  of  a  city,  and  sometimes  a  very  small  section  of  it,  while  it 
fails  to  present  itself  at  all  in  other  sections  of  the  same  city,  and  in  these  localiza- 
tions it  exhibits  a  remarkable  indifference  to  topographical  and  social  surroundings." 

(7)  "In  the  dissemination  of  yellow  fever,  atmospheric  air  is  the  usual  medium 
through  which  the  infection  is  received  into  the  human  system." 

ETIOLOGY  OF  EPIDEMICS. 

The  development  of  an  epidemic  of  yellow  fever  in  places  removed  from  the  endemic 
foci  of  the  disease  depends  upon  :  («)  the  introduction  of  the  specific  cause  by  yellow 
fever  patients,  or  through  infected  articles— fomites ;  (h)  local  conditions  which 
favor  the  multiplication  of  the  specific  germ  external  to  the  body;  (c)  favorable 
meteorological  conditions  ;  (d)  the  presence  of  susceptible  individuals  in  the  infected 
locality. 

We  quite  agree  with  the  board  of  experts  above  quoted  in  the  following  conclu- 
sions also :  (31)  "The  most  frequent  agency  in  the  dissemination  of  yellow  fever 


58      ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

from  place  to  place  is  found  in  yellow  fever  patients  ;  and  more  epidemics  of  yellow 
fever  have  resulted  from  the  introduction  into  previously  exempt  places  of  persons 
sick  of  the  disease,  or  falling  sick  after  arrival,  than  from  all  other  causes.  To 
what  extent  tlie  body  of  the  sick  person  is  responsible  for  this  result,  and  to  what 
extent  his  clothing  and  baggage  is  responsible  for  it,  is  not  known." 

The  last  clause  in  the  above  quoted  conclusion  shows  that  the  board  of  experts 
admitted  the  possibility  that  the  yellow  fever  patient  acts  simply  as  a  carrier  of  the 
infections  agent  about  his  person  or  in  his  baggage.  The  fact  that  he  has  yellow 
fever  is  evidence  that  he  comes  from  an  infected  locality,  and  he  may  be  instrumental 
in  establishing  a  new  center  of  infection  for  this  reason,  rather  than  because  he  is 
himself  a  victim  to  the  disease.  This  is  a  possibility  which  should  not  be  lost  sight 
of;  but,  reasoning  from  analogy  and  from  known  facts  it  seems  extremely  probable — 
indeed  we  may  almost  say  certain — that  the  sick  establish  new  centers  of  infection 
because  the  infectious  agent  is  reproduced  in  their  bodies  and  is  contained  in  their 
excreta. 

That  infected  centers  may  be  established  independently  of  the  arrival  of  sick  per- 
sons is,  however,  beyond  question.  A  striking  instance  of  this  is  afforded  by  an  out- 
break which  occurred  in  Madrid  in  1878.  A  circumscribed  epidemic  was  developed 
in  this  city  about  the  1st  of  September,  which  resulted  in  a  mortality  of  35  out  of 
50  cases  taken  sick.  This  outbreak  was  traced  to  importation,  although  all  of  the 
cases  occurred  among  the  permanent  residents  of  the  infected  area.  Associated  with 
the  young  people  who  first  fell  sick,  crowded  in  the  same  rooms  with  them  to  the 
number  of  10  or  15  in  a  room,  were  a  number  of  soldiers  recently  returned  from  Cuba, 
wiih  Iheir  laggage.  These  men  had  themselves  suffered  from  yellow  fever  in  Cuba,  or 
were  acclimatized  by  long  residence  there. 

We  have  on  record  instances  which  appear  to  be  authentic,  of  the  development  of 
an  epidemic  as  a  result  of  the  opening  of  a  trunk  containing  infected  clothing,  sent 
from  a  locality  where  the  disease  was  prevailing  to  one  previously  healthy.  Epidemics 
have  also  been  traced  to  the  unloading  o(  earlh  ballast  from  the  shores  of  an  infected 
port  upon  the  wharves  of  a  healthy  place  in  the  yellow  fever  zone. 

The  first  cases  of  local  origin  in  an  epidemic  do  not,  as  a  rule,  occur  until  some  time 
has  elapsed  after  the  arrival  of  th-e  infected  ship  or  fomites  or  sick  person  resfionsi- 
ble  for  the  introduction  of  the  "germ."  This  interval  may  vary  from  a  few  days  to 
several  weeks,  according  as  local  conditions  are  favorable  or  otherwise  for  the  devel- 
opment of  the  infectious  agent. 

In  the  great  epidemic  of  1878,  which  was  traced  by  Dr.  Choppin,  president  of  the 
Louisiana  State  board  of  health,  to  importation  by  the  steamship  Emihi  B.  Souder, 
which  arrived  from  Havana  on  the  23d  of  May,  the  first  cases  of  local  origin  did  not 
occur  until  after  an  interval  of  5  or  6  weeks.  But  these  first  cases  occurred,  accord- 
ing to  Dr.  Choppin,  in  the  immediate  Ticinity  of  the  houses  in  which  two  of  the 
officers  of  the  Souder  (Clarke,  the  purser,  and  Elliott,  one  of  the  engineers)  died  soon 
after  the  arrival  of  that  vessel. 

The  local  conditions  which  favor  the  development  of  the  exotic  germ  are  A^arious: 
(a)  Latitude.  Our  account  of  the  geographical  limits  of  the  prevalence  of  the  disease 
suffices  to  show  the  influence  of  latiti,ide,  which  appears  to  be  simply  a  question  of 
temperature.  (6)  Altitude.  The  facts  do  not  justify  the  conclusions  that  the  limita- 
tions as  to  altitude  depend  solely  npon  the  lower  temperature  of  elevated  regions. 
As  pointed  out  by  Hirsch,  "  the  disease  stops  short  at  many  points  in  the  West  Indies, 
where  the  climate  is  still  in  the  highest  degree  tropical.  On  the  other  hand,  there 
have  been  epidemics  in  cool  weather  at  very  considerable  altitudes,  as,  for  example,  at 
Newcastle,  in  .Jamaica"  (elevation  aboiit  4,000  feet).  In  the  Antilles  the  disease  has 
rarely  appeai'ed  at  a  height  of  more  than  700  feet.  In  Mexico  it  has  prevailed  at 
Cordova  (2,500  feet),  but  it  is  unknown  in  the  cities  of  Orizaba,  Jalapa,  and  Pnebla, 
which  have  an  elevation  of  more  than  3,000  feet.  In  Spain  a  single  limited  outbreak 
has  occurred  at  Madrid,  which  is  about  2,000  feet  above  the  sea  level ;  but  with  this 
exception  the  altitudinal  range  has  rarely  exceeded  1,000  feet.     In  the  United  States 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER.  59 

the  most  elevated  locality  in  which  the  disease  has  prevailed  as  an  epidemic  is  Chat- 
tanooga, Tenn.,  which  is  745  feet  above  the  sealevel.  (c)  Yellow  fever  is  essentially 
a  disease  of  the  seacoast,  and  while  in  great  epidemics  it  may  become  widely  diffused 
in  the  interior,  it  follows,  for  the  most  part,  the  course  o£  navigable  rivers,  (d)  It  la 
a  disease  of  cities  and  towns  of  considerable  size,  and  rarely  extends  to  small  country 
villages,  or  among  the  scattered  rural  population.  (e)  In  seajjort  towns  it  frequently 
makes  its  first  appearance  in  the  vicinity  of  the  wharves,  or  in  localities  frequented  by 
sailors.  (/J  Above  all  it  is  a  disease  which  is  influenced  by  local  unsanitarij  conditions. 
Id  those  places  where  it  is  endemic  it  haunts  the  low  lying  and  filthy  portions  of  the 
town,  and  in  epidemics  it  exhil)its  a  marked  preference  for  towns  which  are  in  an 
unsanitary  condition.  It  frequently  happens  that  when  a  town  is  invaded  the  dis- 
ease is  limited,  for  a  considerable  time  at  least,  to  the  filthy  portions  of  the  place,  in 
which  the  degraded  victims  of  poverty  and  vice  congregate  in  ill-ventilated  apart- 
ments, surrounded  by  the  filth  which  accumulates  in  such  localities  when  not  kept 
under  a  rigid  sanitary  supervision,  (g)  Decomposing  organic  matter  of  animal  origin 
seems  to  furnish  an  especially  favorable  nidus  for  the  germ.  This  is  shown  by  its 
favorite  haunts  and  by  the  fact  that  in  marshy  places  in  the  vicinity  of  cities  where 
it  prevails,  and  where  vegetable  decomposition  is  active,  it  does  not  eftect  a  lodg- 
ment. On  the  other  hand,  the  influence  of  putrefying  organic  matter  of  animal 
origin  in  the  production  of  epidemics  has  several  times  been  made  apparent. 

Dr.  Parkes,  the  famous  Euglish  hygieuist,  maintained  the  fecal  origin  of  the  dis- 
ease, and  there  seems  to  be  good  reason  for  the  belief  that  the  accumulation  of  this 
kind  of  filth  in  exposed  situations  is  favorable  to  ttie  development  of  an  epidemic. 

Conditions  relAtmg  to  soil  and  geological  formation  have  not  been  shown  to  influ- 
ence in  an  essential  manner  the  development  or  dift\ision  of  the  disease.  On  the 
other  hand,  the  numerous  epidemics  which  have  occurred  on  shipboard  show  that 
the  disease  is  quite  independent  of  such  conditions,  and  at  the  same  time  disprove 
the  theory,  so  vigorously  maintained  by  numerous  authors  during  the  first  half  of 
the  present  century,  that  the  disease  is  due  to  emanations  of  the  same  nature  as 
those  which  produce  the  so-called  "malarial  fevers."  Meteorological  conditions  con- 
trol  in  a  most  decided  manner  the  prevalence  of  the  disease  in  localities  where  it  is 
endemic,  and  its  epidemic  extension  when  new  infected  centers  are  established  among 
a  susceptible  population.  The  influence  of  temperature  is  shown  by  the  fact  that  it 
is  a  disease  of  the  tropics  and  of  hot  seasons :  that  it  prevails  throughout  the  year  in 
the  cities  of  Rio  Janeiro,  Havana,  and  Vera  Cruz,  although  to  a  much  less  extent 
during  the  cool  season:  while  in  more  temperate  regions  its  prevalence  is  limited  to 
the  summer  season.  It  does  not  prevail  as  an  endemic  disease  in  places  which  have 
a  mean  winter  temperature  much  below  65°,  and  as  a  rule  epidemics  are  not  devel- 
oped at  a  lower  temperature  than  75^  to  80-  F.  The  approach  of  cool  weather  checks 
the  progress  of  an  epidemic,  and  it  is  arrested  completely  when  the  temperature  falls 
to  the  freezing  point.  There  are,  however,  numerous  facts  which  indicate  that  the 
infectious  agent  is  not  destroyed  by  a  freezing  temperature,  altliough  rendered  inac- 
tive. Epidemics  which  have  been  checked  by  frost  have  been  revived  by  the  recur- 
rence of  warm  weather,  and  in  certain  instances  in  temperate  regions  the  germ  has 
survived  the  winter,  and  a  second  epidemic  has  occurred  without  a  new  importation 
(Memphis,  1878-79;  Cadiz,  1800-'01 ;  Malaga,  1808-'O9).  Epidemics  which  originate 
early  in  the  season  often  terminate  before  there  is  frost,  simply  because  the  suscepti- 
ble material  is  exhausted  ;  but  when  strangers  venture  within  the  infected  area  they 
furnish  cviilence  of  the  continued  activity  of  the  morbific  poisou  by  falling  victims 
to  the  disease.     The  influence  of  season  is  shown  by  the  following  tables : 


60 


ETIOLOGY    AND    PREVENTION    OF    Yl!t,LOW    FEVEE. 


Mortalifij  from  i/eUoic  fever  in  Bio  Janeiro  during  the  year  1886. 


Month. 


Total 
deaths 


Mean 
tempera- 
ture. 


Total 
rainfall. 


January  . . . 
February  .  - 

March 

April 

May 

June 

Jnly    

August 

September. 

October 

Kovember  . 
December. . 


135 

234 

347 

220 

48 

18 

.9 

2 

0 

1 

0 

1 


Total I     1,015 


77.5 
70.3 
77.5 
75.0 
G9.  2 
G7.3 
05.  5 
05.5 
08.5 
09.2 
72,9 
74.1 


1.03 
10.91 
3.02 
8.81 
0.35 
1.68 
1.55 
.5.37 
4.59 
1.37 
1.37 
8.92 


49.00 


Mortaliiy  from  yellow  fever  in  Bio  Janeiro  from  January,  IQ'A  to  July,   1870.  (Hirseli.) 


Epidemic  season. 


Nonepidemic  season. 


January 1,118     July 

February 1,760  j  Ausrist 

March 1,  732  |  September  . 

April 1,434     October 


242 
164 
108 
104 


May 

996 

November 

116 

June 

557 

December 

223 

Total 

7,097 

Total 

957 

80  per  cent. 

11  per  cent. 

Alorkilily  from  yelloiv  fever  in  the  city  of  Havana  for  ten  years,  1870  to  1879,  inclusive. 
{Chaille,  report  to  national  hoard  of  health.) 


Month. 


J  anuary 

Febniai-y  .. 

March 

April 

May 

June 

Jnly ,. 

August 

September . 

October 

November  . 
December.. 

Total 


1870. 


4 
6 
14 
66 
112 
201 
91 
77 
49 
35 


1871. 


18 

23 

12 

54 

91 

201 

234 

138 

72 

55 

51 

42 


1872. 


1873. 


32 

23 

27 

37 

127 

378 

41 G 

127 

35 

28 

5 

9 


I,  244 


1874. 


7 

4 

18 

22 

85 

172 

361 

41 G 

180 

91 

42 

21 


1875. 


16 
10 
32 
34 
32 
142 
187 
144 
102 
100 
105 
82 


1, 425  1,  001 


24 

24 

29 

33 

103 

292 

675 

250 

97 

42 

31 

19 

1,619 


1877. 


16 
143 
249 
285 
234 
185 
150 

76 


1878. 


26 

13 

5 

28 

53 

184 

504 

374 

179 

106 

53 

34 


1, 374  1, 559 


1879. 


11 

13 

6 

13 

40 

237 

475 

417 

148 

44 

31 


1,444 


Average 
often 


17 

14 

15 

24 

57 

188 

328 

242 

120 

78 

GO 

40 


Tlie  above  tables  sliow  ns  that  temperature  is  only  one  of  several  factors  uliicli 
control  the  prevalence  of  the  disease,  for  with  a  tolerably  uniform  temperature 
(luring  a  series  of  j'cars,  at  Vera  Cruz,  for  example,  we  have  some  years  marked  by  a 


ETIOLOGY    AND    PKEVENTION    OF    YELLOW    FEVER. 


61 


very  considerable  mortality,  e.  g.,  1875, 1861,  aud  others,  in  which  but  few  cases  occur, 
even  during  the  hottest  part  of  the  season,  e.  (j.,  1869,  1870,  1879.  Again,  it  happens 
that  after  a  summer  of  almost  complete  exemption  an  epidemic  is  developed  in  the 
autumu  which  runs  through  the  entire  winter  (1880-'81).  An  important  factor  which 
does  not  usually  appear  in  statistical  tables  relates  to  the  number  of  susceptible  Indi- 
viduals present  at  difterent  times.  The  arrival,  for  example,  of  emigrants  or  of 
bodies  of  unacclimated  troops  at  Havana  or  Vera  Cruz  would  almost  inevitably  bo 
followed  by  a  marked  increase  in  the  mortality  from  yellow  fever. 

Although  the  development  of  an  epidemic  seems  to  require  a  comparatively  high 
temperature  (75°  to  80'^),  experience  shqws  that  it  may  continue  in  full  force  at  a 
much  lower  temperature  (60-  to  70-')  when  local  conditions  are  faA-orable  and  a  sus- 
ceptible population  is  exposed  in  the  affected  area.  A  good  example  of  this  is 
given  by  the  epidemic  at  Chattanooga,  Tenn.,  which  city  was  invaded  for  the  first 
time  in  1878.  We  obtain  our  data  from  a  paper  by  Dr.  J.  H.  Vandeman,  late  of  the 
Marine  Hosjutal  Service. 

The  first  imported  case,  a  refugee,  was  taken  sick  August  17,  died  August  21. 
The  first  case  among  the  residents  of  the  city  occurred  over  3  weeks  later  (Septem- 
ber i:j),  and  proved  fatal  on  September  19.  The  further  progress  of  the  epidemic 
and  the  mean  temperature  for  each  week  are  shown  in  the  following  table: 

Epidemic  at  Chattanooga,  Tenn.,  in  1878. 


Week  ending — 


September  27 
October  4  ... 
October  11  . . 
October  18  .. 
October  25  . 
November  1. 
November  8 . 
November  15 


New 
cases. 


40 

47 
144 
99 
74 
30 
9 
2 


Deaths. 


iff- an 

teiijpera- 

ture. 


79.71 
70.  42 
06.66 
63.14 
56.52 
48.60 
53.04 
51.83 


Here  we  have  an  ei^idemic,  which  was  at  its  acme  when  the  temperature  was  below 
the  mean  temperature  of  the  winter  months  in  Eio  Janeiro,  Havana,  or  Vera  Cruz. 
The  monthly  mean  temperature  in  the  last-named  city,  and  the  mortality  for  each 
mouth  for  a  period  of  four  years,  are  given  in  the  following  table  : 

Mortality  in  the  city  of  Vera  Cruz  for  four  years. 


Months. 


1878. 


Beat   h 


Mean 
tempera- 
ture. 


Deaths. 


Mean 
tempera- 
ture. 


1880, 


Deaths. 


Mean 
tempera- 
ture. 


1881. 


Deaths. 


Mean 
tempera- 
ture. 


January  . . 
February . 

March 

April 

May 

June 

July 

August ... 
September 
October  . 
November 
December. 


16 
5 
0 
1 

7 
58 
114 
110 
62 
45 
24 
7 


69.5 
72.0 
76.0 
80.5 
84.3 
86.9 
85.6 
84.6 
83.4 
81.2 
77.3 
70.2 


72.9 
72.8 
78.9 
79.0 
88.4 
83.5 
85.6 
86.5 
80.7 
79.0 
79.0 
73.4 


73.2 

75.3 
78.1 
80.8 
84.9 
80.4 
87.0 
86.2 
83.3 
77.5 
76.7 
74.7 


28 

22 

29 

29 

94 

233 

132 

39 

22 

25 

18 

4 


67.3 

67.4 
75.4 
77.1 
82.5 
84.6 
88.1 
87.6 
84.3 
80.6 
75.3 
73.6 


62  ETIOLOGY    AND    PEEVENTION    OF    YELLOW    FEVER. 

An  inspection  of  the  above  table  shows  that  after  an  epidemic  in  the  summer  of 
1878,  whicli  may  be  said  to  have  lasted  from  June  to  December,  two  seasons  of  com- 
parative immunity  followed,  which  cau  not  be  ascribed  to  a  lower  temperature. 
Indeed,  the  average  temperature  for  the  six  months  from  April  to  Seiitember,  inclu- 
sive, was  somewhat  less  in  lt;80  than  in  the  epidemic  years  1678  and  1881.  Again, 
■we  see  that  in  18S0,  after  an  unusually  healthy  summer,  yellow  fever  i)revailed  to  a 
considerable  extent  during  the  mouths  of  October,  November,  and  December,  al- 
though the  teu}perature  was  less  than  during  the  corresponding  months  of  the  pre- 
ceding year.  The  epidemic  impetus  continued  during  the  following  year,  attaining 
its  maximun  of  intensity  in  the  months  of  May,  June,  and  July,  although  in  two  of 
these  months  (May  and  June)  the  temperature  was  lower  than  in  the  corresponding 
mouths  of  the  preceding  healthy  summer. 

Another  factor  of  importance  in  the  etiology  of  yellow  fever  epidemics  is  atmos. 
pheric  moisture  and  preci])itation.  Yellow  fever  is  a  disease  of  the  seacoast  and  of 
the  margins  of  great  rivers,  and  it  does  not  jirevail  in  arid,  desert  places  in  the 
interior,  although  the  elevation  may  be  but  little  above  the  sea  level,  and  the  tem- 
perature extremely  high.  There  is  reason  to  think  that  this  difterence  is  largely  due 
to  the  ditfereuce  as  to  the  moisture  in  the  atmosphere  and  in  the  soil.  Some  authors 
have  insisted  especially  ujjon  the  presence  of  mois  ure  iu  the  atmosphere  almost  to 
the  point  of  saturation  as  an  essential  condition  for  the  development  of  an  epidemic. 
But,  on  the  other  hand,  epidemics  have  occurred  in  unusually  dry  seasons,  as  at  New 
Orleans  in  1841.  In  Martinique,  according  to  Dutrouleau,  yellow  fever  has  some- 
times committed  its  greatest  ravages  after  and  during  the  dryest  seasons. 

La  Roche  states  that  the  epidemics  in  Philadelphia  were  "connected  in  most 
instances  at  least  with  a  deficiency  of  atmospheric  and  terrestrial  humidity — though 
in  all  instances  of  its  occurrence  it  will  be  found  that,  prior  to  the  accession  of  dry 
weather,  the  earth  had  been  more  or  less  saturated  with  rain."  As  pointed  out  by 
this  author,  "  the  coexistence  of  a  clear  atmosphere  is  often  seen."  The  fact  seems 
to  be  that,  while  a  certain  amount  of  moisture  is  essential,  the  limits  vary  consider- 
ably. In  general,  it  may  perhaps  safely  be  said  that  the  degree  of  humidity  and 
the  temperature  most  favorable  for  the  rapid  decomposition  of  organic  material, 
which  forms  the  nidus  in  which  the  infectious  agent  multiplies,  are  the  most  favorable 
for  the  epidemic  extension  of  the  disease. 

Heavy  rains,  by  purifying  the  air  and  cleansing  the  streets  and  seweis  of  an  in- 
fected city,  exercise  a  favorable  eifect  upon  its  sanitary  condition,  and.  in  the  tropics 
the  commencement  of  the  rainy  season  often  puts  an  end  to  the  prevailing  epidemic. 
It  is  probable  that  the  statement  made  hy  some  authors,  that  upon  the  coast  of 
Guiana,  and  elsev\-here  in  the  tropics,  dry  weather  is  favorable  to  the  spread  of  the 
disease,  is  but  another  way  of  stating  the  fact  that  the  heavy  rains  of  tropical  regions 
are  unfavorable,  the  dry  weather  being  only  dry  by  comparison. 

In  the  north  temperate  zone  southerly  winds  are  favorable  to  the  progress  of  an 
epidemic,  because  of  the  elevated  temperature  which  accompanies  them,  and,  on  the 
contrary,  northerly'  winds  have  a  tendency  to  arrest  it.  Fresh  sea  breezes,  and  es- 
pecially the  trade  winds  in  the  tropics,  by  reason  of  their  constancy,  are  beneficial 
from  a  sanitary  point  of  view.  They  dilute  and  carry  away  the  poisonous  emana- 
tions from  the  foul  and  narrow  streets  of  infected  cities  and  refresh  and  invigorate 
the  population. 

There  is  no  evidence  that  the  infectious  agent  of  yellow  fever  cam  be  conveyed  by 
the  wind  in  an  active  condition  to  any  considerable  distance,  and  the  wind  has  but 
little  to  do  with  the  dissemination  of  the  disease.  In  cities  the  extension  of  an 
epidemic  from  centers,  resulting  from  the  importation  of  cases  or  fomites,  is  usually 
quite  gradual  and  independent  of  the  prevailing  currents  of  air.  The  board  of  ex- 
perts appointed  by  Congress  to  investigate  the  epidemic  of  1878  arrived  at  the  fol- 
lowing conclusion: 

"  We  know  of  no  instance,  either  from  our  own  observations  or  from  the  published 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER,  63 

records  of  yellow  fever,  iu  which  it  has  beeu  established  that  the  disease  has  heea 
carried  to  any  considerable  distance  by  atmospheric  currents,  or  by  any  modes  or 
■vehicles  of  conveyance  other  than  those  connected  with  human  traffic  and  travel." 

In  the  comparatively  small  and  landlocked  harbor  of  Havana  vessels  which 
anchor  some  distance  from  shore  and  which  are  kept  in  a  good  sanitary  condition 
do  not  sulFcr  from  yellow  fever  unless  unacclimatized  members  of  the  crew  are  per- 
mitted to  go  on  shore. 

Vessels  lying  at  the  wharves,  on  the  contrary,  are  very  likely  to  become  infected. 

There  are,  however,  numerous  instances  iu  wliich  vessels  have  become  infected 
from  the  shore  or  from  other  vessels,  or  in  which  yellow  fever  has  appeared  iu  places 
lying  to  the  leeward  of  infected  vessels,  in  which  the  transmission  of  the  disease  has 
been  ascribed  to  the  agency  of  the  wind.  It  is  difficult  to  decide  to  what  extent  this 
explanation  is  correct,  for  we  would  have  to  be  sure  that  no  direct  communication 
had  occurred  before  accepting  it;  and  the  possibility  that  the  infection  may  be  con- 
veyed to  the  shore  by  infected  articles  thrown  overboard,  in  the  case  of  infected  ves- 
sels anchored  to  the  windward  of  healthy  places,  must  be  borne  in  mind. 

PROPHYLAXIS. 

What  has  beeu  said  as  to  the  etiology  of  yellow  fever  indicates  clearly  enough  the 
measures  of  prophylaxis  to  be  takeu  in  localities  subject  to  invasion.  These  are :  (a) 
Exclusion  of  the  exotic  germ  of  the  disease  by  the  sanitary  supervision,  at  the  port 
of  departure,  of  ships  sailiug  from  infected  ports,  and  their  thorough  disinfection 
at  the  port  of  arrival  when  there  is  evidence  or  a  reasonable  suspicion  that  they 
are  infected  ;  (6)  isolation  of  the  sick  on  shipboard,  at  quarantine  stations,  and,  so  far 
as  practicable,  in  recently  infected  places;  (c)  disinfection  of  excreta,  and.  of  the 
clothing  and  bedding  used  by  the  sick,  and  of  localities  into  which  cases  have  been 
introduced  or  which  have  become  infected  in  any  way  ;  (d)  de/popidaHon  of  infected 
places,  i.  e.,  the  removal  of  all  susceptible  i^ersous  whose  presence  is  not  absolutely 
necessary  for  the  care  of  the  sick. 

The  time  quarantine  of  former  days,  which  proposed  to  exclude  the  disease  by  de- 
taining ship  and  passengers  at  a  quarantine  station  for  a  fixed  period  of  time  after 
its  arrival,  irrespective  of  its  sanitary  condition,  and  if  yellow  fever  occurred  on 
board  to  quarantine  the  vessel  for  a  certain  number  of  days  .ifter  the  occurrence  of 
the  last  case,  has  been  found  unreliable  and  has  been  pretty  generally  abandoned. 
The  modern  method  of  exclusion  which  relies  upon  the  sanitary  supervision  of  the 
ship  at  the  port  of  departure  and,  so  far  as  practicable,  while  in  transit,  and  upon 
isolation  of  the  sick  and  disinfection  of  the  vessel  when  cases  of  yellow  fever  have 
occurred  on  board  at  a  quarantine  station  provided  with  the  appliances  for  doing 
tins  in  an  effective  manner,  has  proved  far  more  successful.  Reliance  upon  a  time 
quarantine  is  unsafe  for  the  reason  that  the  vessel  may  remain  infected,  for  an  indef- 
inite period  of  time  after  the  occurrence  of  cases  on  board,  or  even  independently  of 
any  case,  if  she  has  been  at  the  wLarves  of  an  infected  port.  No  more  cases  occur 
after  all  of  the  passengers  and  crew  susceptible  to  the  disease  have  suffered  an 
attack,  and  it  may  happen  that  there  are  no  susceptible  i^ersons  on  board;  but  the 
vessel  is  none  the  less  infected'  and  dangerous  to  the  inhabitants  of  the  port  which 
admits  her  to  pratique  without  a  thorough  disinfection.  On  the  other  hand  if  we 
are  to  trust  to  the  measures  indicated  the  sooner  they  are  put  into  execution  the 
better. 

Depopulation  of  infected  ships  or  towns,  when  yellow  fever  makes  its  appearance 
during  the  epidemic  season,  is  a  measure  of  great  importance,  which  should  be  car- 
ried out,  when  practicable,  under  proper  medical  supervision.  It  has  often  hap- 
pened, especially  upon  naval  vessels,  that  the  well  are  retained  upon  the  infected 
ship  and  the  sick  sent  to  a  hospital  on  shore,  under  the  idea  that  the  chief  dauger 
lies  in  contact  with  the  sick.     This  is  a  serious  mistake,  and  has  resulted  in  the  loss 


64      ETIOLOGY  AND  PKEVENTION  OF  YELLOW  FEVEE. 

of  many  lives.  lu  the  United  States  Army  it  is  well  understood  tliat  all  susceptible 
well  persons  are  to  be  removed  to  a  healthy  locality  as  soon  as  yellow  fever  is  known 
to  have  eiiected  a  lodgment  in  quarters  occupied  by  troops.  It  has  been  found  by 
experience  that  a  move  into  camp  checks  the  progress  of  the  disease  among  the  gar- 
rison, although  this  may  be  established  but  a  few  miles  from  the  infected  barracks. 

In  the  case  of  towns  in  a  country  subject  to  invasion  by  the  disease  depopulation 
often  occurs  in  a  way  which  is  most  dangerous  to  other  communities.  It  very  often 
happens  that  the  nature  of  the  disease  is  not  at  first  recognized  even  by  the  physi- 
cians, and  when  recognized  the  hope  is  cherished  that  it  will  not  become  epidemic 
uutil  a  considerable  mortality,  or  the  death  of  some  prominent  citizen,  arouses  the 
fears  of  the  people  and  a  general  "stampede"  occurs.  The  attempt  has  often  been 
made  to  shut  in  the  people  of  an  infected  town  by  means  of  a  "sanitary  cordon," 
composed  of  armed  guards.  This  procedure  is  not  only  inhumane,  so  far  as  the  sus- 
ceptible inhabitants  of  the  place  are  concerned,  whom  it  is  proposed  to  compel  to 
runiain  within  the  infected  area,  but  it  is,  as  a  rule,  futile;  for  when  a  frightened 
man  desires  to  escape  from  an  unseen  enemy  it  is  difficult  to  keep  him  in  a  place  not 
surrounded  by  insurmountable  walls,  or  by  an  impassable  barrier  of  some  kind. 

At  the  International  Sanitary  Conference  of  Eome  (18H5)  the  following  resolution 
was  adopted,  with  a  single  dissenting  vote — that  of  the  delegate  from  Turkey : 

6.   "Land  quarantines  and  sanitary  cordons  are  useless." 

This  related,  it  is  true,  to  cholera,  but  it  applies  as  well  in  the  case  of  yellow 
fever.     Another  resolution,  adopted  at  the  same  conference,  is  to  this  etfect : 

84.  "The  measures  recommended  against  cholera  are,  in  general,  applicable  to 
yellow  fever  and  to  other  diseases  which  prevail  in  epidemic  form,  under  the  iuflu- 
euce  of  bad  sanitary  conditions,  and  which  are  transmitted  by  human  intercourse. 

"The  most  eifective  measures  for  preventing  the  propagation  of  diseases  of  this 
class  are : 

"The  sanitary  improvement  of  cities  and  of  vessels  sailing  from  infected  ports, 
isohition  of  the  sick,  and  disinfection  of  infected  or  suspected  articles  and  localities.''  ■ 

In  yellow  fever  we  require,  in  addition  to  this,  depopulation  of  the  infected  locali- 
ties whenever  it  is  practicable,  and  this  should  be  effected  systematically,  and  with 
due  precautious  to  prevent  the  transportation  of  infectious  material  to  other  places. 

Of  all  measures  of  prophylaxis,  those  which  relate  to  the  sanitary  improvement  of 
cities  and  towns  liable  to  become  infected  are  perhaps  the  most  important.  Munici- 
pal hygiene  has  made  great  strides  since  the  early  part  of  the  present  century,  and 
it  is  probably  to  this  fact,  more  than  to  any  other,  that  certain  Northern  cities  which 
formerly  sutfered  severely  from  yellow  fever  epidemics  owe  their  long  immunity 
from  such  visitations — e.  (/.,  New  York  and  Philadelphia. 

Individual  jirophylaxis  requires  the  individual,  tirst  of  all,  to  avoid  infected  locali- 
ties. If  it  is  absolT.tely  necessary  for  a  susceptible  person  to  visit  a  place  where 
yellow  fever  is  prevailing,  or  to  remain  in  one  in  which  it  has  efiected  a  lodgment, 
he  should  observe  the  following  precautions :  Keep  away  from  low-lying  and  filthy 
portions  of  the  city;  avoid  the  vicinity  of  the  wharves,  and  all  localities  known  to  be 
centers  of  infection,  especially  at  night;  sleep  as  far  from  the  ground  as  possible; 
avoid  excesses  of  all  kinds,  aud  especially  in  the  use  of  alcoholic  drinks  ;  keep  out  of 
the  sun  during  the  hottest  part  of  the  day,  and  bs  careful  not  to  become  overheated 
by  violent  exercise;  avoid  constipation. 

With  reference  to  the  method  of  prophylaxis  by  inoculation,  practiced  in  Brazil  by 
Dr.  Domingos  Freire,  and  in  Mexico  by  Dr.  Carmona  y  Valle,  the  writer,  after  a  care- 
ful examination,  has  reported  ofBcially  that — 

"There  is  no  satisfactory  evidence  that  the  method  of  inoculation  practiced  by  Dr. 
Domingos  Freire  has  any  prophylactic  value. 

"The  claims  of  Dr.  Carmoua  y  Valle,  of  Mexico,  to  have  discovered  the  specific 
cause  of  yellow  fever  have  likewise  no  scientific  basis,  and  he  has  failed  to  demon- 
strate the  protective  value  of  his  proposed  method  of  prophylaxis." 


ETIOLOGY    AND    PEEVENTION    OF    YELLOW    FEVER.  65 


INCUBATION. 

The  period  of  incniiation  iu  yellow  fever  does  Dot  usually  exceed  4  or  5  days,  and 
may  be  less  than  24  hours.  Instances  of  a  much  longer  period  of  incubation  have  been 
given  by  various  authors — even  as  long  as  G  weeks  or  2  months— but  we  are  satisfied 
that  these  are  due  either  to  error  in  diagnosis  or  to  the  fact  that  the  cases  resulted  from 
the  establishment  of  a  new  and  unrecognized  center  of  infection.  Those  who  believe 
that  the  disease  is  only  comiuuiiicated  by  personal  contagion  naturally  date  the  ex- 
posure to  the  latest  date  when  such  personal  contact  was  possible.  Thus,  when  a 
first  case  occurs  on  a  ship  at  sea,  two  or  three  weeks  after  leaving  an  infected  port, 
the  period  of  incubation  is  supposed  to  be  at  least  this  long.  On  the  contrary,  the 
attack  is  due,  in  all  probability,  to  the  fact  that  the  ship  is  infected,  and  the  first  case 
will  probably  be  quickly  followed  by  others  which  have  no  direct  connection  with  it, 
but  result,  as  it  did,  from  exposure  on  the  infected  vessel.  Instances  of  an  attack 
occuring  within  24  hours  after  arrival  in  a  city  where  the  disease  was  prevailing  as 
an  epidemic  are  numerous  and  well  authenticated.  Dr.  Rush  says  in  his  account  of 
the  ex>idemic  of  1793 :  "The  seeds  of  the  disease,  when  received  into  the  body,  were 
generally  excited  into  action  in  a  few  days.  I  met  with  several  cases  iu  which  they 
acted  so  as  to  produce  a  fever  on  the  same  day  on  which  they  were  received  into  the 
system."  During  the  eijidemic  at  Gibraltar,  in  1804,  strangers  were  in  several  in- 
stances attacked  on  the  second  or  third  day  after  lauding,  and  some  are  said  to  have 
been  seized  on  the  first  day.  According  to  Drs.  Pariset,  Balby,  and  Fraugois,  the 
period  of  incubation  at  Barcelona,  in  1821,  appeared  very  short.  "  We  have,"  they 
say,  "  very  strong  reasons  to  suspect,  and  these  reasons  are  founded  on  facts,  that 
this  period  does  not  exceed  24  hours,  or  3  days  at  most."    (La  Roche.) 

In  the  epidemic  at  Fort  Barrancas,  Fla.,  in  1875,  the  writer  had  an  opportunity  to 
fix  the  limits  of  the  period  of  incubation.  The  whole  garrison  was  exposed  in  the 
infected  locality,  and  a  number  of  cases  had  occurred  when  the  command  was  re- 
moved into  camp  in  a  healthy  place  across  the  bay,  near  Fort  Pickens.  On  the  day 
following  the  removal  7  cases  were  sent  back  from  the  camp  for  treatment  in  hos- 
pital. The  next  day  11  cases  came  from  the  camp,  the  following  day  2,  and  the  fifth 
day  2.  The  remnant,  consisting  of  48  individuals,  remained  in  good  health  until  a 
month  later,  when  2  cases  again  occurred  in  camp.  We  do  not  believe  that  these  2 
cases  represent  a  prolonged  period  of  incubation,  but  suppose  that  in  the  interval  the 
camp  had  also  become  infected. 

It  is  proper  to  state  that  several  authors  who  have  had  great  experience  believe 
that  the  period  of  incubation  may  be  extended  to  14  or  even  more  days.  (Blair, 
Rush,  Feraud.) 

CLINICAL  HISTORY. 

As  a  rule,  an  attack  of  yellow  fever  is  not  preceded  by  any  well-marked  j;rc»io«(7ory 
symjjtoms.  The  attack  may  occur  at  night  in  one  who  went  to  bed  in  his  usual  state 
of  health,  or  in  the  early  morning,  after  an  uninterrupted  sleep,  or  during  the  day, 
while  engaged  in  ordinary  occupations.  In  other  cases  there  is  a  feeling  of  lassitude 
and  discomfort  for  two  or  three  days  prior  to  the  attack,  with  loss  of  appetite,  slight 
pain  in  the  back  and  loins,  a  feeling  of  giddiness  or  slight  headache,  flatulent  eructa- 
tions, constipation,  a  tendency  to  perspire  at  night  or  upon  very  slight  exertion,  and 
more  or  less  muscular  debility,  together  with  a  disinclination  for  any  mental  exer- 
tion. 

Dr.  Wragg,  who  had  charge  of  the  Roper  Hf)spital,  at  Charleston,  during  the  epi- 
demic of  1854,  made  particular  inquiries  with  reference  to  premonitory  symptoms, 
and  states  that  "out  of  a  total  of  225  cases  the  attack  was  sudden  in  92;  in  32  it 
came  on  insidiously,  the  patient  complaining  of  malaise,  etc.,  for  a  considerable  time; 
and  that  101  offered  the  usual  symptoms  characterizing  the  ai^ijroach  of  fever. 
40G7 5 


6G  ETIOLOGY  AXD  PREVENTION  OF  YELLOW  FEVER. 

The  attack  is  commonly  inaugnrated  -witli  a  more  or  less  decided  chill,  which  hy 
its  violence  and  duration  affords  some  indication  of  the  probable  severity  of  the  case. 
In  certain  grave  forms  of  the  disease,  however,  the  onset  is  insidious,  and  is  not 
marked  by  any  perceptible  chill.  In  a  considerable  proportion  of  the  mild  cases 
also,  especially  in  the  tropics,  there  is  no  rigor,  and  the  patient  exiieriences  at  most 
only  a  slight  sensation  of  coldness,  which  quickly  gives  place  to  that  of  heat.  If  a 
thermometer  is  placed  in  the  axilla  during  the  initial  chill  it  will  be  found  that  the 
temperature  is  already  considerably  above  the  normal,  and  very  fre<iuently  it  reaches 
the  highest  point  obtained  during  the  eutire  attack  within  a  few  hours  from  its  in- 
ception. 

Accompanying  the  chill  are  other  nervous  phenomena,  similar  in  kind  to  those 
attending  the  onset  of  other  specific  febrile  diseases.  There  is  ciphalalgla,  often  very 
severe,  and  located  by  preference  in  the  forehead  and  supraorbital  region ;  the  eyeballs 
also  are  x>ainful,  and  there  is  intolerance  of  light  in  some  instances,  tain  in  the  Joins  is 
a  very  constant  and  early  symptom,  which  occasions  much  distress,  and  sometimes 
extorts  groans  and  cries  from  the  patient.  At  the  same  time  pain  is  usually  experi- 
enced in  the  lower  extremities,  often  of  a  very  severe  character,  constituting  the 
coup  de  harre  of  the  French  authors ;  it  affects  especially  the  calves  of  the  legs,  the 
knees,  and  the  ankles.  These  symptoms  continue  and  are  even  aggravated  after  the 
rigor  has  passed  and  the  febrile  stage  is  fully  develoj)ed.  In  the  meantime  fheface  be- 
comes liushed  and  sometimes  deep  red  and  swollen  in  appearance ;  the  eyes  are  shin- 
ing and  suffused,  the  coujunctivfc  more  or  less  hypenemic  and  often  deeply  injected, 
in  severe  cases  presenting  a  fiery,  inflamed  appearance,  which  is  accomjiauied  by 
photophobia;  the  skin  becomes  hot  and  dry  and  there  is  apt  to  be,  especially  in  pa- 
tients of  a  nervous  temperament,  great  restlessness  and  jactitation. 

Systematic  authors  have  described  numerous  varieties  of  the  disease,  but  these 
are  for  the  most  part  simjdy  different  grades  in  the  degree  of  severity,  or  depend 
npon  individual  peculiarities  and  complications.  Yellow  fever  is  the  same  in  all 
parts  of  the  world  where  it  occurs,  and  every  great  epidemic  furnishes  exathples  of 
the  several  varieties  which  have  been  described.  It  will  suffice  here  to  mention 
the  classification  adopted  by  one  or  two  standard  authors.  La  Roche  gives  an 
account  of  the  clinical  history  of  the  disease  under  the  following  headings  :  Inflam- 
matory species,  including  three  grades,  intense,  mild,  and  ephemeral ;  congestive 
species,  including  four  grades,  aggravated,  adynamic,  walking,  and  apoplectic. 
Bcranger-Feraud,  in  his  elaborate  account  of  the  disease  as  it  prevails  at  Martinique, 
classifies  the  cases  as  follows : 

First  (lefjree. — Mild  yellow  fever. 

Second  degree. — I'^ellow  fever  of  moderate  intensity  :  («)  cases  in  which  the  onset  is 
frank  :  (h)  cases  in  which  it  is  insidious. 

Tliird  degree. — Grave  yellow  fever :  («)  ordinary  forms,  including  the  gastric,  ad- 
ynamic, ataxic,  congestive,  and  tyiihoid  forms;  (&)  rare  forms,  including  the  hyper- 
esthetic,  gangrenous,  algid  or  choleraic,  and  hydrophobic. 

Fourth  degree. — Y'ellow  fever  siderante. 

Different  epidemics  are  sometimes  characterized  by  the  predominance  of  one  or  tlie 
other  of  the  forms  described,  and  the  character  of  the  disease  as  to  severity  ofteu 
varies  greatly  during  the  same  epidemic.  The  earlier  cases  are  sometimes  mild  and 
the  mortality  small,  while  later  the  greater  intensity  or  malignancy  of  the  poison  is 
shown  by  the  occurrence  of  a  large  number  of  cases  of  the  severest  grade,  and  even 
of  those  rapidly  fa'al  attacks  denominated  by  the  French  siderante. 

It  is  evident,  from  the  account  given  of  the  symptoTus  manifested  at  the  outset  of 
an  attack,  that  these  are  not  sufiSciently  characteristic  to  determine  the  nature  of  the 
disease,  and  in  the  absence  of  a  prevailing  epidemic  its  early  recognition  will  depend 
largely  npon  other  facts  relating  to  the  antecedents  of  the  iiatient,  etc.  The  complete 
clinical  history  of  a  case,  however,  gives  a  tableau  which  is  easily  recognized  by  one 
who  is  familiar  with  the  disease.  In  this  clinical  history  the  thermometric  observ-a- 
tiousform  a  very  important  item. 


ETI0L0C4Y    AND    PREVENTION    OF    YELLOW   FEVER. 


67 


YeUow  fever  is  a  (Usease  of  a  single  febnle  paroxysm,  lastiug  from  48  hours  to  7  or  8 
(lays,  more  commonly  from  3  to  5  days.  The  acme  of  temperature  is  reached  at  the 
outset,  aud  from  this  time  the  temperature  line  is  a  descending  one,  interrupted  some- 
times by  a  slight  evening  exacerbation,  up  to  the  termination  of  the  first  period  of  the 
disease— /fi'^ri/e  stage.  The  second  stage  is  characterized  by  great  prostration  of  the 
vital  powers  aud  lasts  from  a  few  hours  to  2  or  3  Aajs,—stage  of  calm.  The  tempera- 
ture daring  this  stage  sometimes  remains  a  degree  or  more  above  the  normal,  but  mure 
commonly  it  is  normal  or  even  subnormal  for  a  time.  Tbis  is  followed  iu  severe  cases 
by  a  }-e«.cfioHar(//trer  of  irregular  duration  which  presents  a  more  or  less  remittent 
character.     These  features  are  shown  iu  the  accompanying  temperature  charts. 


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Fio.  4568.— Temperature  Carve  of  Yellow  Fever.  1.  Mild  ca.«o  of  brief  duraHon  :  male,  aged  30 :  Fort  Barrancas.  Fl».,  1873  (SternbergV  »■ '^P'"'' 
eovcro  case,  recovered:  ranle,  aired  37;  Fort  Barranc»».  F!«.,  IST)  iStemtvn;).  3.  rrotmctf.l  mild  ciiBe.  recovered;  rajic.  oped  CT  ;  Fort  Bar- 
rancns.  FK  1873  (SterniwrK).  4.  Typical  caae  of  moderate  eeverity.  recovered  :  mnle,  nped  31  .  Fort  Bartoncaa,  fla.,  lf>i  i  (btemOeru).  p  rro 
tractcl  case  of  moderate  eeverity  V  iftgri  moytti'\  recovered  cB6renEor.P.  rand)  B.  Typical  fcvcrc  ca=c ;  protracted  :  death  on  Wtn  naj 
(BirengorPcmnd).  7.  Fatal  C!%se :  death  ou  yth  day,  male,  aged  38;  Fon  naminca.s.  Fla.,  1573  (Sternlxjrg).  8.  Fatal  c 
(B^reDger-Fcraud  l. 


*f7Uirc^  rODWtf  " 


Naturally  the  typical  temperature  curve  is  disturbed  by  complications— visceral 
congestions,  abscesses,  parotitis,  etc.  It  is  also  di.sturbed  by  indiscretions  in  diet, 
overactive  medication,  and  by  moral  causes  (especially  flight  aud  grief).     In  mild 


68  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

cases  the  acme  of  temperature  is  reached  dnriug  the  first  2  or  3  hours  of  the  attack. 
Jn  more  protracted  and  severe  cases  it  is  not  reached  until  the  second  or  third  day, 
rarely  later.  In  an  analysis  of  192  cases  recorded  hy  Faget,  Jones,  and  myself,  the 
acme  was  reached  on  the  first  day  in  102,  on  the  second  in  54,  on  the  third  in  33,  and 
on  the  fourth  in  3.  The  temperature  rarely,  if  ever,  exceeds  108°.  The  highest  tem- 
l^crature  recorded  by  Faget  was  107.2°.  Thornton,  in  a  total  of  143  cases  occurring 
at  Memphis,  noted  a  temperature  of  108  in  a  single  instance.  With  this  exception, 
106.5°  is  the  highest  temperature  recorded  by  him.  In  ray  own  observations  106° 
has  been  the  highest  temperature  noted.  The  teraiieratnre  often  rises  rapidly  just 
before  death,  and  a  very  high  post-mortem  temperature  (108*-'  to  110°)  is  a  common 
phenomenon. 

In  certain  cases  the  initial  paroxysm  is  divided  bj'^  a  more  or  less  complete  remis- 
sion, into  two  or  more  distinct  periods  of  from  2  to  4  days'  duration.  These 
cases,  which  i^ossibly  depend  upon  a  malarial  complication,  are  not  sufficiently  nu- 
merous to  require  a  modification  of  the  general  statement  that  yellow  fever  is  a  con- 
tinued fever  of  a  single  paroxysm.  In  relapses,  which  may  occur  from  imprudence 
at  any  time  after  the  termination  of  the  first  febrile  paroxysm,  the  characters  of  the 
initial  jiaroxysm  are  repeated,  but  in  nonfatal  cases  the  duration  is  usually  not  so 
long. 

Thejra7.se  in  sthenic  cases  is  full,  strong,  and  hard  at  the  outset  of  the  attack,  and 
may  reach  120  or  more  x^ulsations  in  the  minute,  more  commonly  not  more  than  100 
to  110.  It  diminishes  in  rapidity  and  force  as  the  disease  ijrogresses,  and  this  occurs 
even  when  the  febrile  heat  is  not  reduced  lor  2  or  3  days,  and  is  considered  by 
Faget  a  valuable  diagnostic  sign.  During  the  second  stage  of  the  disease  the  pulse, 
however  hard  and  accelerated  it  may  i)reviously  have  been,  becomes  preteruaturally 
slow  and  soft.  The  feebleness  of  the  heart,  which  seems  to  suffer  especially  from  the 
action  of  the  yellow-fever  poison,  and  which  has  undergone  a  certain  degree  of  fatty 
degeneration,  is  shown  by  this  very  compressible  and  slow  pulse,  which  is  often 
reduced  to  40,  and  sometimes  even  to  30  beats  per  minute.  This  constitutes  a  very 
characteristic  feature  of  the  disease,  and  affords  an  important  indication  for  treat- 
ment during  the  period  of  depression,  or  "  calm." 

The /oKf/tte  is  sometimes  but  slightly  coated  at  the  outset,  and  is  usually  moist; 
generally  it  quickly  becomes  covered  with  a  white  coating,  which  may  be  in  streaks ; 
the  margins  as  a  rule  remain  red ;  very  commonly  the  tongue  is  narrow  and  pointed, 
differing  in  this  respect  from  the  broad,  flabby  tongue  of  the  malarial  fevers.  In  the 
progress  of  the  disease  it  often  becomes  dry,  and  the  coating  assumes  a  brownish 
color,  or  it  may  become  very  foul  and  loaded  with  sordes. 

The /ace  is  at  first  flushed  or  bright  red  and  sAvollen,  or  it  maybe  of  a  dusky  violet 
hue ;  this,  with  the  deep  red  suffusion  of  the  eyes  in  severe  cases,  is  quite  character- 
istic. The  countenance  often  has  an  expression  of  anxiety  or  pain,  or  of  dejection  ; 
again  it  may  appear  dull  and  indifferent. 

In  the  last  period  of  the  disease,  in  fatal  cases,  the  features  become  shrunken — 
sometimes  bloated  and  flabby  ;  the  brows  are  often  contracted,  and  the  eyes  sunken, 
with  ecchymosed  lids. 

Thehypem^mia  of  the  conjunctiva?  in  mild  cases  maybe  temporary  ;  in  the  more 
severe  ones  it  is  apt  to  last  through  the  first  period,  and  in  quickly  fatal  cases  the 
eyes  may  be  deeply  injected  throughout.  Usually,  by  the  third  day  a  careful  inspec- 
tion will  show  that  the  conjunctivte  have  a  yellowish  tinge,  which  becomes  more 
intense  as  the  disease  progresses. 

The  sliin  is  hot  and  dry  in  some  cases  throughout  the  first  period ;  in  others  it  soon 
becomes  moist  and  there  is  a  tendency  to  free  perspiration,  Avhich  is  readily  induced 
by  covering  with  blankets,  warm  drinks,  etc.  Even  in  those  cases  in  which  the  skin 
is  hot  and  dry  the  termination  of  the  first  period  is  marked  by  a  soft,  cool,  and  usu- 
ally moist  surface.  In  exceptional  cases  the  skin  remains  hot  and  dry  up  to  the  fatal 
termination.     When  death  occurs  in  the  stage  of  depression,  the  sujf  ace  becomes  cold 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  69 

and  often  is  covered  witli  a  clammy  sweat.  Many  aiithois  have  spoken  of  a  peculiar 
odor  given  off  from  the  surface,  of  yellow-fever  patients,  and  various  attempts  have 
been  made  to  define  its  character  by  comparison  with  other  known  odors.  Dr.  Rush 
said  that  it  resembled  that  of  the  "  washings  of  a  gun."  Dr.  Jackson  describes  it  as 
"  sickly  and  faint,  and  not  unlike  the  smell  of  a  fish  market." 

The  color  of  the  skin,  which  has  given  name  to  the  disease, is  not  always  seen,  but 
usually  a  yellow  discoloration  begins  to  make  its  appearance  toward  the  end  of  the 
first  period,  aud  later  becomes  more  intense,  lasting  for  some  time  after  convalescence 
is  established.  It  varies  much  in  intensity,  from  a  slight  yellow  tinge  to  a  deep  orange 
or  safiron  color.  In  certain  cases  the  skin  presents  a  mahogany  color,  or  that  of 
bronze.  In  fatal  cases  the  yellow  color  is  developed  immediately  after  death,  even  if 
it  has  not  been  very  noticeable  before  dissolution  took  place. 

The  proportion  of  cases  in  wJiich  this  yellow  color  of  the  skin  is  observed  varies 
greatly  in  different  epidemics,  and  even  in  different  periods  of  the  same  epidemic. 
Dr.  Rochonx  states  that  in  the  West  Indies  it  is  absent  in  about  half  of  the  cases 
that  recover.  Bereuger-Feraud,  referring  to  this  statement,  says  that  there  are  in 
fact  two  kinds  of  icterus  in  yellow  fever,  the  one  due  to  blood  pigment,  denominated 
by  Professor  Uubler  liccmaplieiquc  ;  the  other  to  bile  pigments,  and  called  by  the  same 
author  Mlipheique.  The  first  is  considered  by  Ferand  to  be  constant  and  characteris- 
tic; it  occurs  at  a  time  when  the  urine  is  albuminous  and  free  from  bile,  and  mani- 
fests itself  about  the  beginning  of  the  second  stage  by  a  yellow  tinge  of  the  con- 
junctiva?, of  the  face,  and  of  the  skin  over  the  great  vessels.  It  coincides  with  the 
period  during  which  the  htemorrhagic  tendency  of  the  disease  mani fests  itself.  Tlio 
other  form  of  icterus  appears  at  the  end  of  the  second  period,  or  during  convales- 
cence, at  a  time  when  the  urine  contains  a  notable  quantity  of  bile  pigments;  it 
gives  rise  to  the  deep  orange  or  saffron  color  of  the  skin  which  is  so  striking,  but 
which  only  occurs  in  a  certain  proportion  of  the  cases,  and  can  not  be  considered  an 
essential  character  cf  the  disease.  We  are  disposed  to  think  that  Ferand  is  quite 
right  in  this  account  of  the  icterus  of  yellow  fever.  A  slight  yellow  discoloration  of 
the  conjuuctivte  can  commonly  be  detected  during  the  second  stage,  even  in  mild 
cases  in  which  no  discoloration  of  the  skin  is  perceptible. 

Various  skin  eruptions  have  been  described  as  occurring  occasionally,  but  there  is 
nothing  characteristic  about  any  one  of  them  unless  it  is  the  erythematous  eruption 
about  the  scrotum  which  Berenger-Feraud  believes  to  be  pathognomonic  of  the  dis- 
ease. Other  eruptions  mentioned  as  occurring  occasionally  are  petechia,  vesicular 
and  pustular  eruptions,  livid  spots  aud  vibices,  erythematous  patches  about  the  knees 
and  elbows,  or  a  general  erythematous  eruption,  papular  eruptions,  pustules  about 
the  mouth,  furuncles,  etc. 

The  urine  in  yellow  fever,  even  during  the  first  period,  is  reduced  in  amount  below 
the  normal  standard.  This  marked  reduction,  and  in  fatal  cases  very  commonly  com- 
plete suppression,  is  a  notable  feature  of  the  disease. 

The  presence  of  albumen  in  greater  or  less  amount  is  a  symptom  which  is  so  con- 
stant that  it  has  come  to  be  generally  accepted  as  one  of  the  pathognomonic  features 
of  the  disease. 

The  diminution  in  the  amount  of  the  urinary  secretion  in  connection  with  the  amount 
of  albumen  present  is  of  importance  in  a  prognostic  sense,  as  it  is  to  a  certain  extent 
an  index  of  the  gravity  of  the  attack. 

The  most  marked  diminution  occurs  during  the  stage  of  depression,  and  the  few 
ounces  secreted  during  the  24  hours  in  severe  cases  are  loaded  with  albumen  to  such 
an  extent  as  to  form  coagula  Avhich  occupy  one-half  to  two-thirds  of  the  contents  of 
the  test  tube. 

In  a  series  of  observations  made  at  Fort  Barrancas,  Fla.,  in  1875,  to  ascertain  the 
amount  and  specific  gravity  of  the  urine  in  nonfatal  cases  of  yellow  fever,  the 
writer  arrived  at  the  following  results: 

The  amount  considered  in  connection  with  the  specific  gravity  is,  of  course,  au 


70      ETIOLOGY  AND  PEEVENTION  OF  YELLOW  FEVER. 

index  of  the  total  solids  excreted.  In  the  table  wc  liave  eliminated  from  the  speciQc 
gravity  column  the  constant  factor,  1,000.  The  aiuoiint  for  the  first  day  is  no  doubt 
too  small,  on  account  of  the  urine  having  been  only  partly  collected.  It  will  be 
noted  that  the  amount  increases,  while  the  specific  gravity  diminishes,  from  the  out- 
set of  the  attack  up  to  the  time  of  complete  convalescence. 

Taking  the  average  of  sixteen  non-fatal  cases,  I  obtained  the  following  results; 

[Aiuount  iu  fluid  ounces  X  spociflc  gravity —  1,000.] 

Amt.      B.a. 

First  day 8  X  23  =  184 

Second  day 11.  5  X  25  =  287 

Third  day 16  X  28  =  448 

Fourth  day 18  X  22  =  396 

Fifth  day 19  X  22  =  418 

Sixth  day 20  X  22  =  440 

Seventh  day .' 22  X  21  =.  4G2 

Eighth  day 22  X  19  =  418 

Ninth  day 23  X  16  =i  368 

Tenth  day 28  X  13  =  364 

Eleventh  day ,. 37  X  11  ^  407 

Twelfth  day 41  X  13  =  533 

It  will  be  seen  that  the  product  of  the  amount,  multiplied  by  the  spccilic  gravity, 
is  tolerably  uniform  from  tlie  third  to  the  twelfth  day,  and  that  tins  uniformity  is 
preserved  by  a  daily  falling  off  of  the  specific  gravity  to  compensate  for  the  daily 
increase  in  quantity.  To  ascertain  the  product  of  amount  multiplied  by  specific 
gravity  in  patients  convalescent  from  yellow  fever  at  a  later  date,  I  had  the  nrine 
passed  by  sixteen  convalescents,  on  full  diet,  who  had  been  ont  of  bed  from  ten  to 
twenty  days,  preserved  and  measured.  The  result  was  that  the  average  of  amount, 
multiplied  by  the  specific  gravity  for  the  sixteen  cases,  was  491 — a  product  but  little 
in  excess  of  that  obtained  during  the  continuance  of  the  fever  when  the  patients  were 
quiet  in  bed.  The  figures  iu  the  table  may  then  be  taken  as  representing,  approx- 
imately, the  normal  quantity  of  urinary  solids  w^hich  should  be  excreted  daily  dur- 
ing the  progress  of  an  attack  of  yellow  fever,  and  if  the  amount  falls  materially 
below  these  figures,  defective  excretion  may  bo  p)remised,  and  treatmeni  and  prog- 
nosis governed  accordiugly. 

In  mild  cases,  only  a  slight  trace  of  alhmnen  may  be  found  in  the  urine  for  a  day 
or  two,  but  usually  the  deposit  is  sufficiently  abundant  after  the  second  day  to  leave 
no  doubt  as  to  its  character;  it  becomes  more  abundant  at  tlje  termination  of  the 
first  stage,  aud  in  severe  cases  throughout  the  stage  of  calm,  at  which  time  sui^pres- 
sion  is  very  liable  to  occur,  especially  if,  as  a  result  of  exposure,  the  cutaneous 
transpiration  is  checked.  The  early  appearance  and  abundant  presence  of  albumen 
is  generally  recognized  as  an  evil  prognostic.  The  reappearance  of  albumen,  after 
it  has  ovice  disappeared,  iudicates  a  relapse. 

The  amount  of  urea  euminated  by  the  kidneys  is  less  than  normal,  and  in  inverse 
proportion  to  the  severity  of  the  attack.  According  to  Cunisset,  the  quantity  is 
generally  in  proportion  to  the  amount  of  urine  secreted,  and  when  the  amount  in- 
creases it  is  a  favorable  symptom.  Uric  acid  is  also  said  by  this  author  to  be  present 
in  diminished  quantity,  but  in  much  less  proportion  than  the  urea.  He  says:  "We 
have  seen  nrine  containing  only  7  grammes  of  urea  per  litre  give  a  relatively 
abundant  deposit  of  uric  acid."  Bile  pigments  usually  appear  in  the  last  days  of 
sickness,  and  their  presence  is  generally  considered  a  favorable  prognostic  sign.  In 
exceptional  cases  the  urine  may  contain  blood,  from  renal  or  vesical  hemorrhage. 
The  urine  in  yellow  fever  almost  invariably  presents  a  decided  acid  reaction. 

The  symptoms  connected  with  the  nervous  sjjutem  are  varied.  In  mild  cases  the 
intellect  remains  undisturbed,  and  only  a  moderate  amount  of  transient  pain  iu  the 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  71 

bead  and  back  marks  the  ouset  of  tlie  attack.  In  severe  cases  the  frontal  headache 
andrachialgia  are  most  distressing,  and  may  last  throughout  the  first  period  of  the  dis- 
ease. This  stage  is  also  one  of  great  restlessness  and  jactitation  ;  the  patient  sleeps 
Lnt  little,  and  his  sleep  is  apt  to  be  disturbed  by  distressing  dreams  ;  the  mind  often 
seems  to  be  in  a  state  of  tension,  the  patient  is  -watchful,  excited,  and  anxious.  lu 
other  cases  the  mind  is  calm,  and  in  others,  again,  there  is  a  condition  of  apparent 
apathy  or  indifference.  Delirium  is  not  a  very  common  symptom  in  yellow  fever, 
and  the  intellect  often  remains  unclouded  throughout,  even  in  fatal  cases.  Some 
cases,  however,  are  attended  with  incoherency  of  ideas,  or  hallucinations,  and  in 
some  there  is  active  delirium.  More  frequently  the  mind  falls  into  a  torpid  condi- 
tion, the  patient  is  somnolent,  and  when  awakened  is  disposed  to  be  taciturn.  A 
certain  number  of  fatal  cases  are  characterized  by  active  delirium,  followed  by  coma, 
and  a  greater  number  hy  coma  gradually  developed.  In  a  limited  number  of  cases 
death  is  preceded  by  convulsions,  and  occasionally  tetanic  symptoms  of  more  or  less 
general  character  have  been  noted.  Among  the  nervous  symptoms  may  be  mentioned 
deep  sighing  respiration,  sometimes  of  a  spasmodic  character.  Naturally  the  resjiira- 
tion  is  increased  in  frequency  during  the  febrile  stage  ;  in  the  stage  of  calm  it  again 
becomes  normal  in  mild  cases,  or  sighing  and  spasmodic  in  those  of  a  graver  char- 
acter. 

There  is  complete  anorexia  during  the  first  stage  of  the  disease,  but  when  the  re- 
mission occuis  patients  are  very  likely  to  desire  food,  and  even  to  insist  upon  having 
it.  Thirst  is  a  constant  symptom  during  the  febrile  stage,  and  also  in  the  second 
period,  especially  when  there  is  frequent  and  coj^ious  vomiting — black  vomit.  The 
bowels  are  commonly  somewhat  constipated  at  the  outset.  In  the  second  period  of 
the  disease  there  is  apt  to  be  more  or  less  diarrhea,  and  in  fatal  cases  a  dark  fluid  is 
often  discharged  from  the  bowels,  resembling  precisely  that  from  the  stomach.  Oc- 
casionally there  is  a  discharge  of  pure  blood,  the  result  of  intestinal  hemorrhage. 
A  choleraic  form  of  the  disease  is  sometimes  met  with  in  which  there  is  profnse 
diarrhea  and  collapse,  similar  to  that  in  the  algid  stage  of  Asiatic  cholera. 

Symi)toms  connected  with  the  stomach  form  a  prominent  ^jart  of  the  clinical  history 
of  yellow  fever.  The  characteristic  black  vomit  which  has  so  much  occupied  the 
attention  of  medical  authors  is  for  the  vulgar  the  most  striking  feature  of  the  dis- 
ease, and  even  many  physicians  reserve  their  diagnosis  in  early  cases  during  an  epi- 
demic until  they  have  had  ocular  evidence  that  the  vomited  matter  is  black.  The 
common  name  of  the  disease  in  Spanish  countries — vomito — refers  to  this  syniptom. 
Yet  in  a  majority  of  the  cases  there  is  no  vomiting  of  black  matter.  Indeed,  this  is 
recognized  as  a  very  grave  symptom,  and  although  a  considerable  number  of  recov- 
eries occur  after  the  characteristic  black  vomit  has  been  ejected,  this  may  be  consid- 
ered an  exception  to  the  general  rule. 

Vomilincj  is  a  common  symptom  during  the  first  period  of  the  disease  ;  sometimes 
the  fluid  ejected  has  a  yellow  color  from  the  presence  of  bile,  but  more  frequently  it 
is  colorless  and  consists  only  of  the  fluids  ingested,  containing,  in  suspension,  a  little 
mucus  from  the  stomach  ;  it  is  almost  always  acid.  In  favorable  cases  vomiting 
ceases  with  the  first  period  of  the  disease ;  in  those  of  a  graver  character,  after  an 
interval,  perhaps,  of  24  hours  or  more,  during  which  there  is  more  or  less  gastric 
distress,  or  a  feeling  of  weight  and  discomfort,  vomiting  again  occurs,  either  of  a 
clear  acid  fluid  or  of  one  of  the  varieties  of  black  vomit.  At  first  the  black  material 
may  be  in  the  form  of  little  flocculi  suspended  m  a  transparent  fluid,  "  coftee-grouud 
vomit,"  and  as  the  case  progresses  the  amount  of  this  material  increases,  until  the 
whole  fluid  appears  to  be  uniformly  black.  Upon  allowing  it  to  stand,  however,  it 
commonly  separates  into  two  portions,  and  it  will  Ijeseeu  that  it  still  consists  of  a  clear 
liquid  with  the  black  matter  in  suspension.  Upon  microscopic  examination  it  will 
be  found  that  the  colored  material  is  made  up  of  little  masses  which  are  not  black, 
but  have  a  yellowish-brown  color.  A  careful  examination  of  recent  specimens  shows 
that  these  little  masses  contain  decolorized  and  more  or  less  deformed  red  blood  cor- 


72  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

puscles  and  graDular  leucocytes,  and  tbat  the  brown  matter  is  diffused  about  these 
agglomerated  cellular  elements  and  the  matrix  of  mucus  in  which  they  often  seem 
to  be  included.  There  is  no  doubt  that  the  black  vojuit  is  due  to  passive  hemorrhage 
from  the  gastric  mucous  membrane,  although  this  has  been  disputed  by  some  recent 
authors— Freire,  Carmoua,  Gibier.  Formerly  it  was  maintained  by  some  that  the 
black  matter  was  a  secretion  from  the  stomach,  and  by  others  that  it  was  "vitiated 
black  bile."  I  have  myself  repeatedly  veritied  the  fact  by  microscopic  examination 
that  it  contains  the  cellular  elements  of  the  blood.  In  certain  cases  there  is  vomit- 
ing of  pure  blood,  resulting  froui  more  active  gastric  hemorrhage.  This  black 
vomit  is  not  always  discharged  during  life,  but  it  is  extremely  rare  not  to  find  it  iu 
the  stomach  after  death. 

The  fact  that  the  gastric  mucous  membrane  is  seriously  involved  iu  this  disease  is 
shown  not  alone  by  the  vomiting,  the  passive  hemorrhage,  and  the  post-mortem 
appearances,  but  also  by  the  constant  feeling  of  discomfort  or  pain  iu  severe  cases, 
and  by  a  marked  tenderness  upon  pressure  over  the  epigastrium. 

Hemorrhage  may  occur  not  only  from  the  mucous  membrane  of  the  stomach  and 
intestine,  but  also  from  that  of  the  mouth,  nose,  bladder,  and  uterus,  and  even  from 
the  eyes  or  ears.  In  some  epidemics  epistaxis  is  quite  common;  it  may  occur  during 
the  first  period  of  the  disease,  but  is  more  frequent  during  the  second,  at  which  time 
the  general  tendency  to  hemorrhage  is  developed.  Next  to  epistaxis,  hemorrhage 
from  the  buccal  mucous  membrane,  and  especially  from  the  tougue,  the  gums,  and 
the  lips,  is  the  most  frequent. 

In  mild  cases  of  yellow  fcA^er,  convalescence  is  quickly  established.  Instead  of 
the  usual  depression  which  marks  the  second  stage  of  the  disease,  thei.patient,  after 
a  fever  of  3  to  5  days' duration,  may  enter  almost  immediately  into  couvalescence, 
and  within  a  week  may  be  ready  to  resume  his  usual  avocations.  But  in  severe  cases, 
convalescence  is  often  slow  and  may  be  interrupted  by  various  compHcai'wns — paroti- 
tis, buboes,  luruncles,  abscesses,  nepatitis,  diarrhea.  Iu  the  army,  experience  shows 
that  but  few  of  those  attacked  are  able  to  resume  their  duties  iu  less  thau  10  days, 
and  a  considerable  number  remain  in  hospital  from  30  to  50  days.  Blair  found  the 
average  number  of  days  during  which  i^atients  were  retained  in  hospital  after  con- 
valescence was  established  to  be  6.5.5  for  mild  cases,  and  7.91  for  grave  cases. 

Belapses  occur  for  the  most  part  during  the  early  period  of  couvalescence,  or  before 
it  is  fairly  established  ;  they  are  generally  regarded  as  even  more  dangerous  than  the 
first  attack.  Occasionally  a  relapse,  or  second  attack,  occurs  as  late  as  from  2  to  4 
weeks  after  the  termination  of  the  febrile  period  of  the  first  attack. 

PROGNOSIS. 

The  prognosis  in  yellow  fever  should  always  be  guarded,  for  not  only  is  it  a  very 
fatal  disease  in  its  severer  forms,  but  cases  which  appear  mild  at  the  outset  may 
suddenly  assume  a  grave  character.  It  is  more  favorable  in  the  case  of  women  and 
children  than  with  men,  and  is  especially  unfavorable  iu  those  of  intemperate  habits, 
and  in  plethoric  persons  who  have  recently  arrived  in  the  infected  locality.  The 
principal  guide  in  forming  a  prognosis  at  the  outset  of  a  case  is  furnished  by  the 
temperature  observations.  When  the  body  heat  does  not  go  above  103"^  to  103i°  F. 
during  the  first  two  days,  a  favorable  result  maybe  anticipated.  Later,  the  amount 
and  character  of  the  urinary  secretion  is  the  most  inqiortant  i)rognostic  indication. 
When  this  is  scanty  and  heavily  loaded  with  albumen,  the  case  is  very  grave,  al- 
though the  general  appearance  of  the  patient  may  be  favorable,  and  he  may  insist 
that  he  is  "all  right"  and  wants  something  to  eat.  On  the  other  hand,  hopes  of  a 
favorable  issue  may  be  entertained  even  in  cases  characterized  by  great  prostration, 
and  in  which  the  hemorrhagic  tendency  is  pronounced,  if  the  urinary  secretion  is 
tolerably  abundant  and  the  quantity  of  albumen  small.  The  throwiug  up  of  black 
vomit  is  by  no  means  a  fatal  sign,  but  as  a  rule  the  i^assive  hemorrhages  which  occur 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


73 


during  the  second  stage  of  the  disease  are  of  grave  import.  Epistasis  occurring 
during  the  first  stage  has  been  considered  by  some  authors  a  favorable  event  (?). 

The  early  appearance  of  jaundice  is  an  unfavorable  sign  ;  as  is  also  frequent  vomit- 
ing and  great  distress  and  tenderness  in  the  epigastric  region.  Intense  and  long 
continued  injection  of  the  conjunctivae,  giving  the  eyes  a  fiery-red  color,  is  unfavor- 
able. Delirium,  great  restlessness  and  jactitation,  and  sighing  respiration,  are  all 
symptoms  which  give  reason  for  anxiety  as  to  the  result. 

The  prognostic  indications  as  furnished  by  temperature  observations  are  shown  in 
the  following  table,  made  by  the  writer,  some  years  since,  from  a  series  of  cases  in 
which  a  complete  and  careful  record  had  been  made : 


Cases  in  wbicli  the  temperature  was— 

No.  of 
cases. 

No.  of 
deaths. 

Percentage 

of  death  to 

cases. 

13 
9 

36 
80 
87 
29 
15 

13 
9 
22 
24 
6 
0 
0 

100 

10G°  107°        

100 

105°  106° 

'.61 

104°  105°  

30 

103°  104° 

*7 

102°— 103° 

101°- 102° 

Total 

269 

74 

27.5 

''Nearlv. 


MORTALITY. 


The  mortality  from  yellow  fever  varies  greatly  in  different  epidemics  and  among 
different  classes  of  the  community. 

Among  the  natives  of  cities  in  which  the  disease  is  endemic,  or  in  which  it  has  fre- 
quently prevailed  as  an  epidemic,  it  may  be  as  low  as  from  7  to  10  per  cent.  One 
reason  for  this  comparativelj^  small  mortality  is  found  in  the  fact  that  a  considerable 
in'oijortiou  of  the  cases  in  such  a  community  are  among  children.  Among  uuaccli- 
mated  adults  the  mortality  ranges  from  20  to  60  per  cent.,  and  under  certain  circum- 
stances even  exceeds  Ihe  latter  figure.  In  the  great  Philadelphia  epidemics  of  the 
last  and  the  beginning  of  the  present  century,  the  mortality  was  from  20  to  80  per 
cent.  In  the  French  Antilles,  according  to  Datrouleau,  the  mortality  during  the 
years  1851  to  1857,  inclusive,  ranged  from  12.9  per  cent,  to  50  per  cent.  Blair  gives 
the  mortality  at  the  Seaman's  Hospital  at  Georgetown  (Demerara)  in  1838  as  19.5  per 
cent. 

At  Vera  Cruz  the  mortality  for  7  years  (1875-1881)  according  to  Dr.  Molina's 
statistics,  was  41.78  percent,  in  the  hospital  for  men,  and  41  per  cent,  in  the.hospital 
for  women.  In  Rio  Janeiro  the  mortality  for  the  year  1870  Avas  17.4  per  cent.  In 
the  epidemic  of  1873  it  was  23.3  per  cent. 

The  mortality  among  the  Spanish  troops  in  Cuba,  according  to  the  statistics  of 
Dr.  Bastarreche,  was,  in  the  year  1855,  24.31  per  cent.,  and  in  the  royal  navy  17.8 
per  cent. 

Dr.  Bemiss  gives  the  mortality  rate  for  the  city  of  New  Orleans,  during  the  great 
epidemic  of  1878,  as  16.66,  and  classifying  the  eases  according  to  age,  has  constructed 
a  table  which  we  have  used  oa  a  preceding  page  (p.  .52). 

The  day  of  death  is  given  by  Berenger-Feraud  as  follows,  in  a  total  of  1,0.59  cases 
occuring  in  the  French  Antilles  : 

Died  on  the  second  day,  16 — 1.5  per  cent. ;  third  day,  56 — 5.3  per  cent. ;  fourth  day, 
141 — 13.4  per  cent;  fifth  day,  165 — 15.7  per  cent.;  sixth  day,  177—16.9  per  cent.; 
seventh  day,  151—14.3  per  cent.;  eighth  day,  89 — 8.5  per  cent.;  ninth  day,  42 — 3.9 


74  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

per  cent.;  tenth  day,  35 — 3.3  per  cent.;  eleventh  day,  28 — 2.6  per  cent.;  twelfth  day, 
34 — 3.2perceut,;  thirteenth  day,  25 — 2.3  per  cent,;  fourteenth  day,  21 — 1.9  per  cent.; 
fifteenth  day,  8 — 0.7  per  cent.;  sixteenth  day,  7 — 0.6  per  cent.;  seventeenth  day, 
13 — 1.2  j)er  cent.;  eij^hteenth  day,  6;  nineteenth  day,  6;  twentieth  day,  7;  twenty- 
first  day,  3;  twentj'-second  day  2;  tweuty-third  day,  5;  twenty-fourth  day,  3; 
twenty-fifth  day,  3 ;  twenty-sixth  day,  5  ;  twenty-seventh  day,  1 ;  twenty-eighth 
day,  1;  twenty-ninth  day,  2;  thirtieth  day,  1;  thirty-lirst  day,  3;  thirty-second 
day,  1;  thirty-third  day,  1 ;  thiity-sixth  day,  1.  This  table  shows  that  67  per  cent, 
of  the  whole  uumher  died  during  the  first  weelv,  and  82  per  cent,  during  the  first  10 
days.  In  a  similar  table  constructed  by  Dr.  B.  A.  Clements,  of  tlie  United  States 
Army,  out  of  a  total  of  111  fatal  cases,  death  occurred,  during  the  first  weeli  in  73x)er 
cent.;  during  the  first  10  days  in  82  per  cent. 

DIAGNOSIS. 

Notwithstanding  the  well-marked  features  of  a  typical  case  of  yellow  fever,  it  very 
often  happens  that  the  early  cases  in  an  epidemic  are  not  recognized,  and  even  in 
fatal  cases,  with  the  assistance  of  an  autopsy,  physicians  not  previously  familiar  with 
the  disease  often  differ  as  to  the  diagnosis.  At  the  outset  of  an  attacli,  indeed,  there 
is  nothing  sufficiently  characteristic  in  the  symptoms  to  euable  even  an  expert  to 
decide  definitely  that  the  case  is  yellow  fever,  although  there  are  certain  indications 
which  may  give  him  a  strong  suspicion  that  it  is.  The  flushed  face,  fiery  red  eyes, 
pointed  tongue,  supraorbital  pain,  rachialgia,  etc.  When  such  a  case  occurs  during 
the  epidemic  prevalence  of  yellow  fever,  or  in  a  stranger  at  one  of  its  endemic  foci,  the 
inference  usually  is  that  the  individual  has  yellow  lever  ;  but  this  inference  is  some- 
times a  mistalie,  and  more  than  oue  stranger  is  sent  to  the  yellow  fever  hospital  (Jura- 
juba),  of  Rio  Janeiro,  who  turns  out  to  have  some  other  febrile  complaint,  sometimes 
one  of  the  eruptive  fevers.  A  case  in  one  of  our  own  seaport  cities,  with  precisely  the 
same  symptoms,  occurring  at  a  time  when  yellow  fever  was  not  prevailing,  would 
almost  infallibly  be  pronounced  ''malarial  fever,"  or  "bilious  fever,"  or  "remittent 
fever,"  as  soon  as  it  was  evident  that  it  was  not  one  of  the  specific  eruptive  fevers. 
And  this  diagnosis  would  very  probably  be  maintained  if  no  evidence  could  be  found 
that  the  individual  had  been  exposed  to  yellow  fever,  even  if  tlie  further  clinical  his- 
tory of  the  case  corresponded  with  that  of  this  disease.  It  is  in  this  way  that  a  series 
of  cases,  occurring  perhaps  in  the  practice  of  several  different  physicians,  at  the  out- 
set of  an  epidemic  are  frequently  called  by  some  other  name.  The  fact  that  the  early 
cases  in  an  epidemic  are  sometimes  of  a  mikl  character  adds  to  the  liability  to  error. 
A  man  has  a  chill  followed  by  fever,  and  receives  in  the  next  48  hours  several  full 
doses  of  quinine;  at  the  end  of  this  time  his  fever  has  disappeared,  and  with  the 
exception  of  a  certain  amount  of  debility,  and  perhaps  an  irritable  stomach,  he  feels 
quite  well.  The  inference  is  that  he  had  an  attack  of  malarial  fever  which  was  cut 
short  by  the  treatment ;  perhaps  it  was  so,  but  tlie  inference  is  the  same  in  "either 
case.  I  have  seen  cases  in  the  hospitals  of  Vera  Cruz,  for  example,  in  which  there 
was  a  slight  amount  of  albumen  in  the  urine,  and  in  wliich  the  depression  ind  slow 
pulse  following  a  single  febrile  paroxism  of  brief  duration  seemed  to  me  to  be  char- 
acteristic of  a  mild  attack  of  yellow  fever,  but  in  which  the  diagnosis  was  malarial 
fever,  and  the  brief  duration  of  the  attack  was  ascribed  to  the  full  doses  of  quinine 
wfiich  had  been  administered.  I  have  seen  precisely  similar  cases  during  the  preva- 
lence of  an  epidemic  of  yellow  fever,  in  which  no  quinine  was  given,  and  in  which,  not- 
withstanding, the  febrile  paroxysm  was  of  brief  duration  and  did  not  return.  For 
example,  the  case  represented  by  tracing  No.  1  in  the  chart.  This  case  by  itself  could 
not  have  been  diagnosed  as  yellow  fever,  but  occurring  as  it  did  with  several  others  of 
the  same  mild  character,  side  by  side  with  severe  and  fatal  cases  of  this  disease,  Idid 
not  doubt  that  it  was  due  to  tfie  same  specific  cause,  and  was  in  fact  a  case  of  yellow 
fever. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  75 

The  occurreuce,  in  a  southern  seaport,  of  a  group  of  cases  of  ephemeral  fever,  in  a 
parMcular  locality,  esiieciallj'  among  the  colored  population,  should  always  arouse 
suspicion  and  lead  to  iuvestigatiou.  When  in  such  a  city,  or  in  any  place  within 
the  limits  of  yellow-fever  invasion,  and  during  the  summer  mouths,  we  hear  that  a 
•'malignant  form  of  malarial  fever"  has  aj)peared  in  a  certain  limited  area,  a  single 
house,  or  square,  or  district,  we  shall  not  be  apt  to  go  wrong  in  the  inference  that  the 
disease  is  yellow  fever.  Malignant  forms  of  malarial  fever  belong  to  the  country 
rather  than  to  the  city,  and  cases  do  not  occur  in  groups  Avithin  city  limits,  where 
the  malarial  poison  is  not  generated  in  its  most  intense  form,  if  at  all.  Formerlj', 
very  much  uncertainty  as  to  diagnosis  arose  from  mistaken  ideas  aa,to  the  etiology 
of  the  disease.  A  considerable  number  of  jihysicians  in  the  United  States  maintained 
that  yellow  fever  and  the  malarial  fevers  are  closely  allied  if  not  identical  diseases, 
due  to  the  same  general  causes,  and  the  idea  was  very  prevalent  that,  under  the  in- 
lluence  of  meteorological  conditions,  a  mild  form  of  malarial  fever  might  be  trans- 
formed into  the  malignant  yellow  fever.  Under  this  idea,  physicians  felt  justified 
in  calling  the  mild  cases  in  an  epidemic  malarial  fever,  and  in  reserving  the  name 
yellow  fever  for  those  in  which  a  yellow  skin,  highlj^  albuminous  urine,  and  black 
vomit  make  u])  the  clinical  tableau  to  which  they  gave  the  name  yellow  fever.  Of  these 
three  prominent  features,  only  one  is  a  constant  character  which  can  serve  in  establish- 
ing the  diagnosis  in  mild  cases.  This  is  the  presence  of  albumen  in  the  urine.  At  some 
period  of  the  disease,  even  in  the  mildest  cases,  there  will  be  a  distinct  trace  of  albu- 
men in  the  urine,  as  skown  by  the  usual  tests,  and  this  will  generally  be  sufficiently 
abundant  to  leave  no  doubt  iu  the  mind  of  the  observer  as  to  the  nature  of  the  pre- 
cipitate. In  61  cases  occurring  during  an  epidemic  in  Jamaica,  Donnet  found  albu- 
men present  for  the  first  time:  In  2  cases  on  the  first  day;  in  11  cases  on  the  second 
day;  in  19  cases  on  the  third  day;  in  14  cases  ou  the  fourth  day ;  iu  6  cases  on  the 
fifth  day ;  in  4  cases  ou  the  sixth  day  ;  in  4  cases  ou  the  seventh  day ;  in  1  case  on 
the  eighth  day.  It  will  be  seen  that  iu  by  far  the  larger  number  of  cases  the  pres- 
ence of  albumen  was  verified  on  the  second,  third,  or  fourth  day.  The  value  of  this 
test  in  the  diff"erential  diagnosis  of  yellow  fever  is  indisputable.  It  is  true  that  a 
trace  of  albumen  is  sometimes  found  in  the  urine  of  severe  cases  of  fevers  of  malarial 
origin,  but  iu  cases  of  yellow  fever  of  ecxual  severity,  as  compared  with  these,  the 
precipitate  would,  as  a  rule,  be  very  abundant  on  the  third  or  fourth  day  of  sickness, 
forming  a  deposit  to  the  extent  of  one-fourtn  to  one- half  the  contents  of  the  test  tube 
or  even  more.  At  the  same  time,  a  microscopical  examination  would  show  the  pres- 
ence of  numerous  granular  casts  from  the  tubuli  uriniferi. 

These  are  found  also,  although  in  a  smaller  number,  iu  the  urine  of  tlie  milder  cases 
during  the  second  stage  of  the  disease.  For  diagnostic  purx^oses  the  character  of 
the  febrile  paroxysm,  and  especially  tke  phenomena  following  this,  which  mark  the 
second  stage  of  the  disease,  are  the  most  important.  The  characteristics  of  the 
temx>erature  curve  are  sufficiently  shown  by  the  charts  of  typical  cases  iu  page  67, 
It  must  be  remembered,  however,  that  while  the  stage  of  depression  is  commonly 
marked  by  a  normal,  or  even  subnormal,  temperature,  in  a  considerable  number  of 
severe  and  fatal  cases  the  temperature  still  remains  a  degree  or  two  above  the 
normal  when  the  cool  skin  and  slow,  soft  pulse  would  indicate,  if  the  thermometer 
were  not  used,  that  there  was  complete  apyrexia ;  or  again,  the  skin  remains  dry, 
and  the  patient  falls  into  a  tyjihoid  condition,  witli  a  fluctuating  temperature, 
without  having  had  a  complete  remission  of  febrile  heat.  The  second  stage  of  the 
disease  is,  however,  commonly  well  marked  in  nonfatal  cases,  and  is  its  most  cha- 
racteristic feature;  the  remarkably  slow  and  soft  pulse,  the  evident  prostration  of 
the  vital  powers,  although,  the  patient  may  be  comfortable  and  even  cheerful,  and 
desirous  of  getting  up,  or  of  taking  food  ;  the  yellow  tinge  of  the  conjunctiva'  and 
skin — not  always  present  ;  the  tenderness  on  pressure  in  the  epigastric  region,  and 
often  a  feeling  of  weight  and  distress  in  this  region,  attended  with  intense  thirst 
and  vomiting  of  a  transparent  acid  fluid,  or  of  the  characteristic  black  vomit;  the 


76  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

fcendeucy  to  passive  hemorrhage  from  the  mucous  surfaces  of  the  mouth  or  uose; 
oozing  of  dark  blood  from  the  gums,  or  lips,  or  sides  of  the  red  and  fissured  tohoue; 
the  scanty  urinary  secretion  aud  the  presence  of  albusieu,  usually  in  considerable 
amount;  all  of  these  symptoms  constitute  an  ensemhh  that  for  the  practiced  eye  and 
hand  is  unmistakable. 

The  dilferential  diagnosis  from  bilious  remittent  fever,  with  which  yellow  fever  has 
frequently  been  confounded,  is  not  always  iiosslble  at  the  outset  of  an  attack,  bnt 
the  contrast  in  the  complete  clinical  history  of  the  two  diseases  is  suflieiently  strik- 
ing. Remittent  fever,  as  the  name  indicates,  is  characterized  by  periodical  remis- 
sions of  the  fehrile  heat;  this  is,  however,  in  severe  cases  often  not  well  marked  so 
far  as  exact  thermometric  observations  are  concerned,  and  is  rather  a  remission, 
usually  occurring  in  the  morning,  of  the  general  symptoms — headache,  vomiting, 
heat  of  surface,  rapidity  of  pulse — than  a  decided  lowering  of  the  body  heat,  as  shown 
l»y  the  thermometer  x)laced  in  the  axilla.  But,  as  a  rule,  an  attack  of  remittent  fever 
is  made  up  of  a  series  of  paroxysms,  each  of  which  may  be  inaugurated  by  a  more  or 
less  distinct  chill;  while  yellow  fever  is  essentially  a  disease  of  a  single  paroxysm, 
in  which,  as  shown  by  our  charts,  the  acme  of  temperature  is  reached  early  in  the  at- 
tack, and  the  remission  is  characterized  by  a  descending  line  extending  often  through 
a  period  of  three  or  four  days.  In  remittent  fever,  on  the  contrary,  the  fall  attending 
the  remission  is  an  abrui)t  one.  The  tongue  in  remittent  fever  is  usually  heavily 
covered  with  a  yellowish  or  brownish  coating,  it  is  broad,  and  often  marked  upon  the 
margins  by  indentations  made  by  the  teeth,  showing  that  it  is  swollen.  In  yellow 
fever  the  tongue  is  usually  narrow  and  pointed,  often  tremulous ;  at  the  outset  of  an 
attack  it  may  be  comparatively  clean,  or  it  is  covered  with  a  thin  white,  or  heavy 
cottony  coating — occasionally  yellowish.  The  yellow  color  of  the  skin  in  bilious  re- 
mittent fever  does  not  differ  from  that  of  simple  jaundice,  and  is  very  persistent 
wheu  developed;  it  is,  however,  far  from  being  a  constant  symptom.  The  same  is 
true  of  the  jaundice  which  is  occasionally  developed  during  convalescence  from  yel- 
low fever.  But,  besides  this,  there  is  a  more  or  less  pronounced  yellow  tinge  of  the 
conjunctiva}  and  skin  in  yellow  fever,  which  appears  during  the  latter  part  of  the 
first,  or  early  in  the  second,  stage,  aud  which  in  convalescence  quickly  disappears. 
In  fatal  cases  this  yellow  color  is  more  pronounced,  and  may  assume  a  dingy  brown 
or  mahogany  color ;  the  dependent  portions  of  the  body  after  death  have  a  livid, 
mottled  ai)i)earauce,  and  the  discoloration  resembles  that  following  a  bruise  which 
has  produced  an  effusion  of  blood.  In  the  malarial  fevers  the  spleen  is  more  or  less 
swollen  and  tender,  while  in  yellow  fever  it  is  not  involved.  In  yellow  fever  the 
intellectual  faculties  are  commonly  unimpaired,  at  least  during  the  febrile  stage,  and 
often  up  to  the  moment  of  the  fatal  termination  ;  ou  the  contrary,  delirium  is  quite 
common  in  severe  attacks  of  bilious  remittent  fever.  In  yellow  fever  vomiting  of 
bilious  matter  is  rare,  and  only  occurs,  if  at  all,  at  the  outset  of  the  attack;  while 
later,  the  vomited  matter  consists  of  the  fluids  ingested,  or  of  a  transparent  acid  fluid 
containing  iiocculi  of  mucus,  or  of  one  of  the  varieties  of  black  vomit ;  in  remittent 
fever  the  vomited  matters  are  nearly  always  colared  with  bile — indeed,  bilious  vom- 
iting is  commonly  a  marked  feature  of  the  disease.  In  remittent  fever,  according  to 
La  Roche,  the  quantity  of  uric  acid  in  the  urine  is  notably  increased,  being  in  somo 
cases  eight  times  as  great  as  in  health  ;  in  yellow  fever  it  is  diminished — the  amount 
of  urea  is  diminished  in  both  diseases.  Suppression  of  urine  is  extremely  rare  iu 
bilious  remittent  fever,  and  extremely  common  in  fatal  cases  of  yellow  fever;  the 
uniform  presence  of  albumen  in  the  latter  disease  has  already  been  noted.  Finally, 
the  marked  hemorrhagic  tendency  in  yellow  fever  distinguishes  this  disease  from 
bilious  remittent  fever. 

There  is  a  form  of  malarial  fever,  however,  the  so-called  "hemorrhagic  mahirial 
fever,"  which  is  characterized  by  the  periodical  appearance  of  blood  pigment  iu  the 
urine,  with  sometimes  a  tendency  to  hemorrhage  from  mucous  surfaces.  This  is  the 
Jievre  hilieuse  melanurique  of  the  French  authors.     The  clinical  history  of  this  disease 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  77 

differs  entirely  from  that  of  yellow  fever.  The  distinguishing  cliaracters  are  given 
by  Bereuger-Feraud  as  follows  : 

"Prolonged  residence  in  a  malarial  country  is  the  most  powerful,  and,  indeed,  in- 
dispensable predisposing  cause. 

"The  disease  is  always  x^receded  by  numerous  attacks  of  malarial  fever,  simple  at 
first,  then  more  and  more  complicated,  and  taking  in  general  more  and  more  of  a 
bilious  aspect,  producing  a  very  decided  anaemia. 

"Icterus  appears  at  the  outset  of  the  attack,  and  is  never  wanting ;  it  gives  from 
the  commencement  and  throughout  the  attack  a  uniform  yellow  color  to  the  patient, 
varyiug  from  greenish-yellow  to  a  decided  yellow  ocher. 

"The  march  is  intermittent  or  remittent  from  the  first,  and  the  pulse,  urine,  and 
vomitiug  follow  very  exactly  the  variations  of  temperature.     *     *     * 

"  The  vomiting  is  bilious,  of  a  decided  green  color;  it  is  a  constant  symptom  at  the 
outset  of  an  attack,  and  is  arrested  with  the  termination  of  one  attack  to  reajipear 
with  the  next. 

"After  the  first,  or  febrile,  period  the  vomiting  continues,  but  preserves  the  same 
characters;  it  stains  linen  a  bright  green,  and  when  collected  in  a  basin  it  appears 
transparent,  and  is  of  a  beautiful  emerald-green  or  olive  color. 

"The  tongue  is  moist,  broad,  covered  at  first  with  a  heavy  white  fur,  which  soon 
receives  a  greenish  tint  from  the  vomited  matters.  The  tongue  is  not  red,  either 
upon  its  tip  or  edges ;  it  remains  broad,  heavily  coated,  and  moist  to  the  end  of  the 
malady. 

"The  urine  is  black  from  the  commencement,  and  its  color  is  characteristic,  so  that 
the  i)atient  himself  is  struck  with  it.  It  is  usually  abundant  and  frequently  passed, 
and  only  has  the  melanuric  aspect  during  the  attack." 

In  malarial  hiematuria,  as  seen  in  this  country,  the  urine  varies  in  color,  according 
to  the  amount  of  blood  pigment  present,  from  a  light  red  to  a  deep  claret,  or  porter 
color.  It  is  usually  acid,  and  always  albuminous.  -The  presence  of  red-blood  cor- 
puscles has  frequently  been  demonstrated  by  microscopical  examination,  and  tube 
casts,  made  up  of  grauular  matter  and  red  corpuscles,  are  often  present  in  the  urine. 
In  the  gravest  form  of  the  disease  the  patient  falls  into  a  typhoid  condition,  and  at 
this  time  epistaxis  is  likely  to  occur,  or  there  may  be,  in  rare  cases,  hemorrhage 
from  the  stomach  or  bowels. 

The  differential  diagnosis  between  yellow  fever  and  dengue  will  depend  maiuly 
upon  the  fatal  character  of  the  tirstmeutioued  disease,  the  presence  of  albumen  in 
the  urine,  and  the  hemorrhagic  tendency,  as  contrasted  with  the  absence  of  these 
features  and  the  skin  eruptions  and  arthritic  paius  in  the  other.  Dengue,  like  mild 
yellow  fever,  often  termiuates,  after  a  febrile  stage  of  48  hours'  duration,  in  com- 
plete apyrexia,  and  the  patients  are  able  to  resume  their  ordinary  occupations, 
although  feeling  stiff  and  sore  when  making  any  movement ;  more  frequently  there 
is  a  return  of  the  fever  attended  by  a  rubeoloid  eruption,  which  ends  in  desquama- 
tion, and  is  accompanied  tvith  a  return  of  the  arthritic  and  muscular  pains.  This 
stage  may  last  but  3  or  4  days,  or  may  be  of  much  longer  duration,  but  in  any  case 
the  disease  is  not  attended  with  danger  to  life. 

The  Mlious  typhoid  of  Griesinger  presents  some  points  of  resemblance  with  yellow 
fever,  but  the  clinical  and  pathological  features  are  sufficiently  distinct  to  make  it 
improbable  that  errors  in  diagnosis  will  occur  when  due  care  is  taken. 

Quite  recently,  Dr.  Diaraantopulos,  of  Smyrna,  has  given  an  account  of  a  disease 
under  the  name  of  iyphuf.  icferoides,  which  is  said  to  be  distinct  from  the  bilious  ty- 
phoid of  the  German  authors,  and  which  prevails  upou  the  coast  of  the  mainland, 
and  upon  the  islands  of  the  iEgean  Sea.  This  name  has  frequently  been  applied  to 
yellow  fever,  which  the  disease  described  resembles  in  mauy  particulars,  although 
no  doubt  distinct  from  it.  It  prevails  in  the  summer  and  autumn.  The  attack 
begins  with  a  chill,  followed  by  fever,  intense  headache,  pain  in  back  and  limbs, 
jactitation,   etc.     The   eyes  are  described  as   injected,   glisteniug,  and  humid;  the 


78      ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

epigastrium  is  tender  on  pressure,  tlie  liver  and  spleen  are  more  or  less  enlarged. 
There  is  a  remission  of  tlie  fever  on  the  third  or  fourth  day,  and  the  second 
stage  is  inangnrated  by  a  general  improvement  in  the  appearance  and  feelings 
of  the  patient;  later  (fifth  or  sixth  day),  icterus  is  developed  ;  this  is  intense,  giving 
to  the  whole  surface  a  golden  or  orange-yellow  color.  Epistaxis  is  frequent  in  this 
stage,  and  hemorrhage  from  the  bowels,  bloody  urine,  aud  petechije  in  certain  cases, 
show  that  the  disease  has  a  hemorrhagic  tendency.  It  is  said  to  prevail  endemic- 
ally,  or  as  an  epidemic,  and  to  be  miasmatic  and  not  contagious.  Perhaps  this  is 
the  same  disease  as  was  epidemic  on  the  island  of  Mauritius  in  18j7,  an  account  of 
which  has  been  given  by  Pelleran  in  the  Archives  de  Medecine  navale  (tome  36,  1881). 
This  author,  after  stating  that  up  to  the  year  1867,  the  opinion  was  generally  enter- 
tained that  malarial  fevers  did  not  exist  in  Mauritius,  goes  on  to  say  that  in  1867 
"the  etfects  were  terrible  and  so  unusual  that  the  epidemic  was  ascribed  to  importa- 
tion." One  of  the  reporters  quoted  by  Pelleran  gives  the  clinical  features  as  follows  : 
"The  patient  fell  suddenly  ill  when  in  perfect  health,  often  after  a  full  meal.  The 
skin  became  hot,  the  face  red,  the  eyes  injected,  the  pulse  mounted  to  90  or  100; 
the  skin  became  yellow,  the  tongue  dry  and  glossy,  perspiration  abundant,  accom- 
panied by  a  cold  breath,  and  exceedingly  feeble  pulse;  afterward  followed  intense 
prostration,  with  intolerable  pain  in  the  back,  loins,  and  region  of  the  liver.  The 
poor  patient  after  20  to  30  hours  died  in  a  state  of  collapse  similar  to  that  of  cholera. 
Another  character  of  the  fever  was  its  tendency  to  relapse,  to  occur  at  all  seasons  of 
the  year,  in  dry,  elevated  localities  as  well  as  in  those  which  were  low  and  dam}),  and 
to  be  accompanied  by  hemorrhages. 

It  is  evident  that  these  fevers,  if  they  prevailed  in  the  same  areas  as  yellow  fever, 
might  give  rise  to  confusion  in  the  diagnosis;  aud  also,  that  our  knowledge  of  the 
pathology  of  tropical  fevers  is  far  from  being  complete. 

Many  of  the  physicians  practicing  in  the  French  Antilles  recognize  a  fever  called 
by  them  fierre  inflammatoire  as  distinct  from  yellow  fever.  Bei-enger-Ferand  has 
shown,  however,  that  it  is  in  fact  identical  with  this  disease,  aud  only  rej)resents  one 
of  its  grades  of  severity. 

TREATMENT. 

The  unsatisfactory  results  obtained  in  the  various  methods  of  treatment  proposed 
are  shown  by  the  fact  that  a  majority  of  the  physicians  in  those  parts  of  the  w^orld 
where  yellow  fever  prevails,  who  have  had  an  extended  experience,  agree  that  active 
medication  is  injurious,  and  have  settled  upon  an  expectant  or  symptomatic  treat- 
ment, with  careful  nursing,  as  giving  the  most  favorable  results.  Y^et  the  records  of 
the  past  show  that  a  certain  jiroportion  of  the  cases  recover  under  all  modes  of  treat- 
ment, even  the  most  active  and  opposed  to  our  present  views.  The  famous  Dr.  Rush, 
of  Philadelphia,  was  thoroughly  convinced  of  the  advantages  of  copious  bleeding  dur- 
ino-  the  first  stage  of  the  disease,  and  ascribed  the  more  favorable  results  obtained  in 
the  epidemic  of  1793  as  compared  with  those  of  1741,  1747  and  1762  to  the  more  liberal 
use  of  the  lancet.  Venesection  was  often  repeated  from  five  to  ten  times  by  Rush  and 
other  practitioners  of  this  date,  and  the  amount  of  blood  extracted  often  exceeded 
100  ounces — 150  and  even  200  in  some  cases.  This  excessive  bleeding  was  soon 
al^andoned,  but  the  propriety  of  drawing  blood  at  the  outset  of  the  attack  was  main- 
tained by  many  practitioners  in  the  United  States  and  the  West  Indies  for  many  years 
after  the  "  heroic ''  treatment  of  Rash  had  been  abandoned,  and  the  statistics  offered 
in  favor  of  this  practice  certainly  compare  favorably  with  the  results  obtained  at  the 
present  day  bj'  expectant  treatment.  Thus  Dr.  Catel,  who  was  in  charge  of  a  mili- 
tary hospital  at  Martinique,  reports  that,  out  of  176  patients  treated  during  the  first 
24  hours  by  bleeding,  .5  only  died — a  mortality  of  1  in  35;  of  108  treated  on  the  second 
day,  11  died,  or  1  in  9;  and  of  143  treated  on  the  third  nay,  40  died,  or  1  in  3.  Dr. 
Lefort,  a  physician  of  the  same  place,  also  reports  that  4  out  of  5  of  those  bled  on 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  79 

the  first  day  recoyerecl,  aud  asserts  that  ou  the  secoud  day  blood-lettiug  affords  six 
times  less  chance  of  success  (La  Roche). 

Tbe  hiucet  has  beeu  entirely  abandoned,  in  accordance  ■with  the  changed  rie'ws  as 
to  the  pathology  of  febrile  affections,  but  it  may  be  questioned  whether  in  the  pleth- 
oric new-comers  in  tropical  regions,  who  furnish  so  large  a  quota  to  the  mortality 
list  from  yellow  fever,  a  single  bleeding  at  the  outset  of  the  attack  might  not  still  be 
liracticed  with  benefit. 

Emetics  were  formerly  considered  an  essential  part  of  the  antiphlogistic  treatment. 
We  speak  of  them  onlj^  to  condemn  them,  except  in  those  cases  in  which  at  the  out- 
set of  an  attack  there  is  evidence  that  the  stoojach  contains  undigested  and  ferment- 
ing material  which  is  the  cause  of  nansea  and  distress.  In  this  case  a  simple  emetic 
may  be  administered,  with  the  sole  object  of  unloading  the  stomach. 

Purgatives  have  at  all  times  been  considered  useful  at  the  outset  of  an  attack  of 
yellow  fever,  and  it  is  the  standard  treatment,  wherever  the  disease  prevails,  to  ad- 
minister a  cathartic  of  some  kind  as  soon  as  the  jiatient  comes  under  observation. 
Opinions  differ  as  to  the  best  form  of  cathartic  medicine;  some  prefer  a  mercurial, 
some  a  saline,  and  others  a  full  dose  of  oleum  ricini.  On  account  of  its  prompt  and 
thorough  action  and  the  absence  of  irritating  properties,  the  last  mentioned  medicine 
is  a  favorite  in  ourown  Southern  cities,  in  theWest  Indies  and  in  Brazil, especially  in  do- 
mestic practice  among  the  Creole  population.  The  dose  usually  given  might  seem 
excessive  to  those  who  have  not  seen  its  favorable  action  ;  half  a  tumbler  full,  or 
even  more,  is  the  common  dose  for  an  adult — 2  to  4  iluid  ounces.  Many  iihysicians 
still  prefer  a  mercurial  purge,  followed,  if  necessary,  by  a  saline  cathartic,  and  calo- 
mel is  the  mercurial  usually  selected.  This  was  formerly  given  by  some  practition- 
ers in  enormous  doses — 40  to  60  grains — for  its  "sedative"  efl'ect,  and  by  others 
in  repeated  small  doses  as  a  "  sallvant."  Dr.  Rush  introduced  the  use  of  mercury  as 
a  sallvant  in  the  treatment  of  yellow  fever  in  the  epidemic  of  1793,  and  "encouraged 
by  the  good  effects  observed  on  that  occasion  from  a  salivation,  he  was  induced  the 
next  year  to  excite  it  as  early  as  possible  in  all  those  cases  which  did  not  yield 
immediately  to  bleeding  and  purging.  He  wasdelight'^d  to  find  that  it  immediately 
attracted  aud  concentrated  in  the  mouth  all  the  scattered  pains  of  every  part  of  the 
body,  checked  nausea  and  vomiting,  and  gradually,  when  it  was  copious,  reduced 
the  pulse,  thereby  preventing  the  necessity  of  further  bleeding  and  purging."  He 
used  mercury  still  more  extensively  in  1797;  and  during  the  memorable  epidemic  of 
1798  a  salivation  Avas  found  by  him  to  be  the  most  certain  remedy  of  any  that  was 
used  in  this  fever,  for  he  "did  not  lose  a  single  patient  in  whom  the  mercury  acted 
upon  the  salivary  glands"  (La  Roche).  It  is  scarcely  necessary  to  remark  that  this 
treatment  has  been  entirely  abandoned,  and  when  calomel  is  given  to-day  it  is  usu- 
ally for  its  cathartic  effect,  or  for  its  supposed  action  upon  the  liver.  It  may  be,  how- 
ever, that  it  is  useful  in  another  way.  As  we  have  Indicated  in  discussing  the  etiology 
of  the  disease,  it  seems  extremely  probable  that  it  is  caused  by  a  microbe  whose  habitat 
is  in  the  alimentary  canal.  If  this  is  in  fact  the  case,  the  indications  are  apparent, 
\\z,  to  keep  the  j^rivue  vice  as  nearly  empty  as  possible,  so  that  the  multiplication 
of  the  specific  microorganism  may  be  restricted  by  want  of  pabulum  ;  and  also  for 
the  purpose  of  removing  the  microbe  and  its  poisonous  products;  second,  the  admin- 
istration of  germicide  and  antiseptic  remedies,  with  a  view  to  the  destruction  of  the 
germ,  or  at  least  of  restricting  its  development.  In  carrying  out  both  of  these  indi- 
cations it  will  be  necessary  to  avoid  any  measures  which  would  induce  gastric  or  in- 
testinal irritation  ;  for,  as  we  have  seen,  the  gastro-intestinal  mucous  membrane  is 
in  a  hypememic  condition  early  In  the  attack,  and  experience  has  demonstrated  that 
this  condition  is  aggravated  by  active  medication,  or  by  the  presence  of  food — even 
the  simplest— and  that  the  gravest  danger  may  result  from  the  administration  of  any 
thing  which  may  add  to  the  irritation  of  the  stomach  or  intestine,  the  normal  func- 
tions of  which  seem  to  be  arrested  as  a  result  of  the  action  of  the  toxic  agent  which 
gives  rise  to  the  morbid  phenomena.     For  this  reason  it  is  necessary  to  administer 


80      ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

cathartics  with  great  caution,  if  they  seem  called  for  after  the  second  day  of  the  dis- 
ease. As  a  rule,  it  will  be  best  to  spare  the  stomach,  and  to  move  the  bowelsby  pur- 
gative enemata. 

The  prevailing  opinion  that  yellow  fever  is  closely  allied  to  the  malarial  fevers 
led  many  physicians,  during  the  first  half  of  the  present  century,  to  prescribe 
quinine  in  the  expectation  that  it  might  prove  a  specific  in  this  disease.  This  ex- 
pectation was  not  fulfilled,  but  there  are  still  a  certain  number  of  experienced 
physicians  who  thiuk  a  full  dose  at  the  outset  of  an  attack  to  be  beneficial ;  others 
consider  it  injurious,  and  as  a  rule  it  has  been  abandoned.  There  is,  however,  much 
evidence  in  favor  of  the  practice,  although  the  benefits  to  be  derived  from  it  have 
no  doubt  been  overstated.  Dr.  Fenner,  in  his  accouut  of  the  epidemic  of  1849, 
states  that  the  results  obtained  in  the  abortive  method  of  treatment  by  quinine  were 
entirely  successful.  The  dose  given  was  from  20  to  30  grains,  with  a  moderate 
quantity  of  morphine  or  opium,  after  having  unloaded  the  bowels  with  a  purgative 
enema.  Dr.  Fenner  says:  "This  would  generally  reduce  the  vascular  and  nervous 
excitement  completely  in  the  course  of  a  few  hours,  throw  the  patient  into  a  profuse 
persoiration,  relieve  all  pain,  and  produce  sleep."  This  is  certainly  a  very  desirable 
result,  and  while  to-day  it  is  generally  admitted  that  quinine  has  no  specific  actiou 
in  yellow  fever,  aud  that  after  the  first  day  or  two  it  is  liable  to  do  barm  by  irritating 
the  stomach,  the  writer  is  disposed  to  thiuk  that,  as  an  antipyretic  and  nervous 
sedative  at  the  outset  of  the  attack,  it  may  often  be  administered  with  advantage. 
This  was  the  conviction  of  some  of  our  most  experienced  army  surgeons  who  en- 
countered the  disease  at  Vera  Cruz  during  the  Mexican  war,  and  subsequently  in 
New  Orleans. 

Dr.  Anderson,  of  Mobile,  who,  with  his  associate  iu  xJractice,  treated  a  large  num- 
ber of  cases  during  the  epidemic  of  1853,  says:  "The  marked  and  almost  magic 
effect  of  a  large  dose  of  quinine  at  the  outset  was  so  apparent  that  they  (himself 
and  associate)  would  have  considered  it  little  short  of  trifling  with  human  life  to 
have  adopted  any  other  treatment.  They  will  not  deny  that  there  were  cases  in 
which  it  did  no  good;  in  fact,  in  those  cases  where  there  was  at  the  commencement 
decided  congestion  of  the  brain,  it  may  sometimes  have  done  harm.'' 

Blair,  whose  experience  was  very  extensive,  and  whose  treatment  seems  to  have 
been  unusually  successful,  gave  20  grains  of  calomel  and  2.5  grains  of  quinine  at  the 
outset  of  an  attack,  and  under  certain  circumstances  repeated  the  dose  several  times. 

Dr.  Porcher,  of  Charleston,  follows  Blair's  treatment  so  far  as  the  first  dose  is  con- 
cerned, but  protests  against  a  repetition  of  it.  "We  think  he  is  quite  right  in  this,  and 
that  his  remarks  upon  treatment  are  extremely  judicious.  In  some  of  the  new  anti- 
pyretics and  nervous  sedatives  we  have  agents  which  are  probably  superior  to  qui- 
nine for  reducing  the  temperature  and  relieving  the  nervous  symptoms;  favorable 
reports  have  already  been  made  with  reference  to  some  of  these.  In  the  epidemic  of 
last  year  (1887)  at  Key  "West,  Drs.  Porter  and  Schweringen  used  aniipyrin,  as  they 
believe,  to  the  advantage  of  their  patients;  it  has  also  been  prescribed  quite  exten- 
sively in  Havana,  but  I  have  seen  no  exact  statements  as  to  the  results  obtained. 
Nageli,  a  German  physician  practicing  in  Rio  Janeiro,  has  given  a  very  favorable  ac- 
count of  results  obtained  in  the  use  of  Jcalrin.  According  to  this  author,  of  seven 
cases  treated  from  the  beginning,  five  of  which  were  severe  (three  had  black  vomit)» 
all  recovered.  The  course  of  the  disease  was  not  shortened,  but  the  fever  is  said  to 
have  been  controlled.  The  medicine  was  administered  from  the  outset  in  doses  of 
1  gramme  every  hour,  in  capsules.  Tliis  treatment  is  said  to  have  quickly  reduced 
the  temperature,  after  three  or  four  doses,  to  38"^  (100.4^  F.)  or  below;  at  the  same 
time  abundant  perspiration  occurred  aud  the  pains  were  relieved.  Doses  of  one-half 
a  gramme  were  given  every  hour  after  the  temperature  was  reduced  to  the  normal  to 
keep  it  from  again  mounting.  Iced  drinks  were  given,  but  no  food  ;  after  the  fourth  or 
fifth  day  it  was  sometimes  necessary  to  increase  the  dose  to  1..')  to  2  grammes  in  order 
to  control  the  return  of  fever.     The  urinary  secretion  continued  during  the  use  of  the 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  81 

remedy,  and  Nageli  thought  that  less  albumen  was  present  than  in  similar  cases  not 
so  treated.  As  the  acconut  of  this  method  of  treatment  was  published  in  1884,  and 
we  have  not  heard  that  it  has  been  adopted  to  any  extent  in  Rio,  the  supposition  is 
that,  like  many  other  methods,  it  has  not  stood  the  test  of  fuller  experience.  In  the 
feeble  condition  of  the  heart  iu  the  second  stage  of  yellow  fever,  we  should  anticipate 
that  the  large  doses  administered,  as  much  as  14  grammes  in  the  24  hours,  might  be 
dangerous;  but  as  all  of  Dr.  Nageli's  patients  are  said  to  have  recovered  we  can  not 
urge  this  objection. 

Many  of  the  French  physicians  administer  6ro»UfZeo/j;otessiMm  as  a  nervous  sedative, 
but  we  anticipate  that  antipyrin,  or  one  of  the  more  recent  remedies  of  this  class, 
will  be  found  the  most  useful  in  meeting  this  indication  and  for  the  reduction  of  tem- 
perature ;  there  is  no  reason  to  expect,  however,  that  they  will  prove  to  be  specif- 
ics— they  simply  meet  certain  indications  in  the  symptomatic  treatment  of  the  dis- 
ease. Some  of  the  physicians  iu  Rio  Janeiro  have  prescribed  _/rt?)orfl?ifZ!,  and  think 
well  of  it,  without,  however,  claiming  that  it  has  any  specific  power.  When  the  skin 
is  hot  and  dry  it  may  serve  a  useful  purpose,  but  it  will  be  necessary  to  guard 
against  the  depressing  eftects  of  the  remedy.  Recently,  Dr.  Hebersmith,  of  the  Marine 
Hospital  Service,  has  given  the  muriate  of  pilocarpin  in  several  cases,  and  he  thinks 
with  good  results.  Doses  of  one-eighth  to  one-fourth  grain  were  given  hypodermi- 
cally,  and  produced  profuse  perspiration,  with  reduction  of  temperature.  But  as  sev- 
eral of  his  cases  were  colored  persons,  and  the  initial  temperature  was  moderate  in 
all,  we  are  not  prepared  to  admit  that  recovery  was  due  to  the  administration  of  this 
medicine. 

Aconite,  digitalU,  and  veratrine  have  been  tested  in  the  West  Indies  and  elsewhere, 
in  full  sedative  doses.  Feraud  says  of  these  medicines  that  "the  attempts,  although 
sufficiently  numerous,  have  not  yet  furnished  any  decided  results."  After  a  careful 
trial  of  digitalis  in  doses  of  2  to  3  grammes  (30  to  45  minims)  of  the  tincture  per  diem, 
the  author  quoted  arrives  at  the  couelusion  that  in  mild  cases  it  seems  to  cause  the 
fever  to  fall  more  quickly,  but  in  intense  cases  it  had  not  the  same  power.  His  gen- 
eral conclusion  is,  that  aconite,  digitalis,  and  veratrine  are  sux^erior  to  quinine,  and 
that  in  moderate  doses  they  are  useful  in  allaying  nervous  excitement,  and  in  moder- 
ating to  a  slight  extent  the  fever.  The  writer  has  been  in  the  habit  of  giving  small 
doses  of  aconite,  in  combination  with  a  mild  diaphoretic,  during  the  febrile  stage  of 
yellow  fever,  and  has  thought  that  some  benelit  was  derived  from  the  treatment, 
although  it  must  be  confessed  that  this  has  not  been  very  marked. 

Dr.  Bemiss,  of  New  Orleans,  writes  of  this  class  of  medicines  as  follows: 

"  It  is  the  practice  of  some  physicians  to  attempt  the  reduction  of  fever  by  lar"-e 
injections  of  cold  water,  which  are  said  to  prove  very  efficient  antipyretics.  Aconite, 
veratrum,  tartrate  of  antimony,  and  ipecac  are  frequently  exhibited.  A  cautious  use 
of  one  or  the  other  of  the  first  two  on  this  list  may  prove  beneficial,  but  their  inju- 
dicious or  careless  exhibition  may  do  irreparable  harm.  We  have  seen  digitalis  produce 
unquestionably  good  effect  inmiiigatin  (J  fever,  and  have  often  administered  it  in  doses  of 
thirty  to  sixty  drops  of  the  tincture  every  third  or  fourth  hour.  It  is  best  to  give  it  in 
solutions  of  acetate  of  ammonia  or  potash." 

Dr.  Porcher,  of  Charleston,  gives  the  following  mixture  as  a  gentle  diuretic  and 
diaphoretic. 

Yy,  Acetate  of  potash,  3  i 
Citrate  of  potash,  3  i 
Morphine,  gr.  j 
Camphor  water,   ^  vi 

M.  A  dessert- spoonful  to  he  given  every  two  or  three  hours  as  long  as  there  is  heat 
of  skin. 

Some  formula  of  this  kind,  which  has  a  gentle  sedative  and  diaphoretic  effect,  is 
useful  so  long  as  it  does  not  disturb  the  stomach.  Many  practitioners  refrain  from 
giving  any  medicine  at  all,  but  permit  the  patients  to  swallow  bits  of  ice,  or  small 
4067 6 


82      ETIOLOGY  AND  PKEVENTION  OF  YELLOW  FEVER. 

quantities  of  ice  cold  water  at  freqneut  intervals.  This  we  quite  approve  of,  or  iced 
carlonic  acid  umler  may  be  given.  Others  again  give  tvarm  drinks  to  promote  perspi- 
ration. This  is  tlie  standard  "  creole  treatmeut "  in  New  Orleans,  and  in  many  parts 
of  the  West  Indies.  As  the  mortality  among  this  class  is  small,  they  are  well  satisfied 
with  the  results  obtained,  but  many  strangers,  unacclimatized,  who  have  received 
the  Creole  treatment,  die,  in  spite  of  the  dose  of  castor  oil,  the  hot  ])ediluvia,  and  the 
orange-leaf  tea.  This  treatment,  with-careful  nursing  is,  however,  infinitely  superior 
to  the  active  medication  of  the  novice  in  the  treatment  of  this  treacherous  disease, 
for  it  is  very  easy  to  kill  yellow  fever  patients. 

Dr.  Pardinas,  formerly  director  of  the  Military  Hospital  in  Havana,  gave  full  doses 
of  the  tr.ferri  cMoridi  throughout  the  disease,  and  without  claiming  for  it  any  specific 
virtues,  he  was  convinced  that  the  mortality  was  less  under  its  use  than  in  other 
methods  of  treatmeut  with  which  he  was  familiar.  The  director  of  the  Jura-juba 
Hospital,  at  Eio  Janeiro,  gave  me  the  following  formula,  which,  after  trying  many 
different  modes  of  treatment,  he  has  adopted  as  being,  in  his  opinion,  the  best: 

1^  Perchloride  of  iron  (normal  solution),  grammes  iv 
Tincture  of  iodine,  gramme  1 
Distilled  water,  grammes  400 

M.  A  tablespoouful  to  be  given  every  hour. 

Some  physicians  in  the  United  States  have  also  iised  the  tincture  of  the  chloride  of 
iron  in  full  doses^  and  have  reported  favorable  results  ;  but  it  has  not  come  into  gen- 
eral use,  even  in  those  places  from  which  the  favorable  reports  have  come.  In  Sa- 
vannah, during  the  epidemic  of  1854,  it  was  prescribed  extensively  by  Drs.  Wildmau 
and  Harris.  The  last  named  physician  reported  that,  out  of  two  or  three  hundred 
cases  treated  in  this  way,  he  only  lost  six.  La  Eoche,  in  commenting  upon  this  re^ 
port,  says:  "  Unfortunately^  the  remedy,  though  so  advantageous  when  administered 
to  the  sufferers  of  Savannah,  was  powerless  in  the  cases  of  those  to  whom  it  owed  its 
celebrity,  for  both  Dr.  Wildmau  and  Dr.  Harris  fell  victims  to  the  i)revailing  epi- 
demic." 

Baths  of  all  kinds — hot,  cold,  tepid,  medicated — have  been  given  in  yellow  fever, 
and  the  evideace  is  varied  as  to  their  utility.  The  most  judicious  and  experienced 
practitioners  are,  however,  in  accord  as  to  the  danger  of  disturbing  the  patient  to 
the  extent  demanded  by  frequent  baths,  and,  as  a  rule,  content  themselves  with  hot 
pcdihiria  at  the  outset  of  the  attack,  and  with  sponging  the  surface  with  cold  water 
or  evaporating  lotions  to  reduce  the  temperature.  Very  hot  or  very  cold  baths  are 
condemned  by  Feraud,  on  the  ground  that  they  are  likely,  even  in  the  first  stage  of 
the  disease,  to  produce  visceral  congestions,  to  which  there  is  a  great  tendency  in 
this  disease.  In  the  southern  part  of  our  own  country,  and  in  the  West  Indies,  a  hot 
mvsiard  foot-hafh,  administered  at  the  outset  of  the  attack,  is  a  standard  method  of 
treatment.  The  patient  is  wrapped  in  a  blanket,  and  sits  with  his  feet  and  legs  im- 
mersed in  a  bucket  of  water  as  hot  as  he  can  bear,  to  which  a  liberal  quantity  of 
mustard  has  been  added.  This  has  a  tendency  to  relieve  cerebral  congestion  and 
headache,  and  often  produces  a  free  perspiration.  It  may  be  repeated  several  times 
during  the  first  24  hours.  Cold  applications  to  the  head  and  repeated  sponging  of 
the  hands,  arms,  and  chest  with  cold  water,  give  comfort  to  the  patient,  and  are  ot 
decided  benefit  on  account  of  their  antipyretic  effect.  Some  practitioners  recommend 
the  use  of  tepid  water  for  siionging  the  surface ;  Feraud  prefers  a  mixture  ot  one 
part  of  aromatic  alcohol  with  three  i^arts  of  water;  Dr.  Peyre  Porcher  recommends 
"  the  assiduous  and  protracted  applications  cf  ice-cold  water  to  the  head,  hands,  and 
arms,  as  long  as  they  are  abnormally  hot."  This  practice  is  justified  by  the  results 
of  his  treatment,  and  we  think  it  entirely  safe  and  extremely  useful.  The  knowledge 
that  exposure  to  cool  currents  of  air,  or  by  removing  the  bed-covers  at  night  when 
the  weather  has  suddenly  turned  cold,  is  attended  with  the  greatest  danger,  on  ac- 
count of  the  visceral  congestions — especially  of  the  kidneys — which  result  from  such 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVEE.  83 

exposure,  lias  led  mauy  physiciaus  to  refrain  from  makiug  use  of  cold  lotions  to  the 
surface.  Tlie  same  apprehension  has  also  led  to  an  excessive  use  of  blankets,  and  the 
poor  patient,  who  is  burning  up  with  fever,  is  sometimes  smothered  in  blankets  and 
carefully  guarded  to  prevent  him  from  exposing  hand  or  foot  to  the  air. 

Towards  the  end  of  the  first  stage,  and  throughout  the  second  stage  of  the  disease, 
this  watchfulness  to  prevent  exposure  of  the  body  to  cool  currents  of  air  is  very  neces- 
sary ;  indeed,  it  is  important  at  all  times  if  the  external  temperature  is  low,  and 
especially  at  eight,  but  the  object  in  view  can  be  obtained  without  loadiog  the  pa- 
tient with  blankets.  He  should  belightly  covered,  but  carefully  guarded  from  expo- 
sure if  the  weather  is  cool.  At  the  same  time  the  body  may  be  spouged  under  the 
blanket,  and  iced  water  applied  to  the  head,  face,  hands,  and  arms,  during  the  febrile 
stage. 

Berenger-Feraud  speaks  highly  of  the  use  of  large  enemata  of  cold  water,  frequently 
repeated,  as  a  means  of  reducing  the  temperature.  He  has  made  extensive  use  of 
this  mode  of  treatment,  and  has  never  geen  any  evil  results  from  it. 

The  use  of  siitainsms  and  vesicants  to  relieve  visceral  congestion  by  revulsion  to  the 
surface  is  approved  by  experienced  physiciaus  everywhere.  We  prefer  sinapisms  and 
believe  that,  as  a  rule,  they  will  accomplish  all  that  can  be  expected  from  a  blister. 
The  feeling  of  weiglit,  distress,  or  absolute  pain  in  the  epigastric  region,  attended 
with  nausea,  which  is  largely  due  to  the  hyperai-mia  of  the  gastric  mucous  membrane  is 
often  notably  relieved  by  the  application  of  a  sinapism  to  the  epigastrium.  The  patient, 
who  has  been  restless  and  uncomfortable,  will  sometimes  quickly  fall  asleep  after 
such  an  application.  In  the  same  way,  cerebral  congestion  and  headache  may  be  re- 
lieved by  revulsives  to  the  extremities,  and  lumbar  pain  by  the  application  of  a  large 
siuai>ism  to  the  loins. 

The  scanty  urinarj^  secretion,  and  often  complete  suppression,  in  yellow  fever,  seems 
to  call  for  the  use  of  diuretics,  but  unfortunately  experience  teaches  that  the  most 
reliable  medicines  of  this  class  do  but  little  good.  The  kidneys  are  best  relieved  by 
those  means  which  promote  iierspiratiou,  and  by  revnlsauts  ai^plied  to  the  loins. 
Comiilete  suppression  is  rarely,  if  ever,  relieved  by  any  plan  of  treatment.  In  cases 
with  a  hot,  dry  skin,  and  scanty  urinary  secretion,  with  lumbar  pain,  indicating  con- 
gestion of  the  kidneys,  we  should  expect  benefit  from  the  hypodermic  administration 
of  the  muriate  of  pilocarpine. 

Stimulants  are  i-arely  required  before  the  fourth  or  fifth  day,  and  must  be  given  at 
first  cautiously  and  in  small  doses,  so  as  not  to  disturb  the  stomach;  later,  however, 
they  are  often  absolutely  demanded  to  sustain  the  feeble  heart.  During  the  second 
stage  of  the  disease,  when  the  pulsations  of  the  heart  often  do  not  exceed  forty  or 
fifty  to  the  minute,  there  is  always  a  tendency  to  syncope;  this  is  especially  mani- 
fested during  the  night  or  toward  morning,  and  many  a  patient  whose  condition 
seemed  satisfactory  at  the  evening  visit  has  been  found  by  his  physician  dead  the 
next  morning.  This  dangerous  period  may  often  be  tided  over  by  the  use  of  stimu- 
lants. When  the  stomach  is  very  irritable,  a  little  iced  champagne  will  often  answer 
better  than  anything  else;  but  perhaps  the  best  form  of  stimulant  is  good  brandy, 
given  in  teaspoouful  doses  at  intervals  of  half  an  hour,  more  or  less,  according  to  cir- 
cumstances. It  should  be  given  ice  cold.  Later,  milk  punch,  English  ale,  or  porter 
may  be  given  in  liberal  quantities,  especially  to  those  who  are  in  the  habit  of  usino- 
spirits. 

Blair,  whose  opinion  in  all  that  relates  to  this  disease  is  worthy  of  attention,  pre- 
fers hock  to  any  other  form  of  stimulant.  He  says :  "Of  all  cordials  the  best  is  Rhen- 
ish wine.  When  of  good  quality  it  is  retained  when  everything  else  is  rejected,  and 
it  is  universally  liked  by  the  patients.  I  have  seen  the  most  excellent  effects  from 
its  use,  and  have  often  given  it  to  the  extent  of  two  bottles  in  twenty-four  hours.  I 
believe  it  has  saved  many  lives,  and  know  of  no  substitute  for  it." 

Medicines  administered  by  the  stomach  to  control  vomiting,  as  a  rule,  are  worse 
than  useless.     Minute  doses  of  morpMve,  administered  hypodermically,  are  sometimes 


84  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

useful  in  checking  gastric  irritability,  but  this  is  a  dangerous  remedy  in  yellow  fever, 
and  only  very  small  doses  are  tolerated.  Blair  lias  seen  stupor,  prostration,  and  com- 
plete narcotism  follow  the  administration  of  one-tenth  of  a  grain.  On  account  of  the 
danger  attending  its  administration,  he  thinks  that  it  will  be  more  judicious  to  place 
it  in  the  index  exi)urgatorius  of  yellow  fever,  Bemiss,  whose  opinion  is  of  equal  value, 
says:  "Voioiting  should  be  met  with  epispastics,  blisters,  ice,  and  small  doses  of 
opium,  in  combination  with  cherry  laurel  water  and  sodte  bicarb."  An  effort  should 
be  made  to  arrest  hiemorrhage  by  the  use  of  ergot,  the  bcMieflcial  effects  of  which  are 
sometimes  well  marked.  As  it  is  not  likely  to  bo  absorbed  by  the  stomach,  aud  may 
cause  vomiting,  it  will  be  best  to  adniiuister  ergotine  hypodermically. 

Duviiig  coivalesencc  the  sulphate  of  quinine,  in  moderate  doses,  or  citrate  of  iron 
and  quinine,  or  the  standard  preparations  of  iron  and  of  strychnine,  will  often  be 
useful  as  tonics  ;  aud  ale  or  porter  or  a  sound  wine  in  moderate  quantities,  will  be 
found  beneficial. 

The  alimentation  in  this  disease,  as  in  the  specific  fevers  generally,  is  a  matter  of 
prime  importance.  During  the  first  part  of  the  febrile  stage  no  food  is  desired,  nor  is  it 
required.  It  is  best  to  give  nothing  in  the  way  of  food  for  the  first  three  or  four  days  of 
sickness;  after  this,  if  the  stomach  tolerates  it,  an  ounce  or  two  of  iced  milk  or  of  chicken 
broth  may 'be  given  every  two  or  three  hours.  If  the  stomach  is  very  irritable,  a 
smaller  quantity  at  shorter  iutervals  may  be  given,  and  it  will  be  best  to  give  the 
milk  in  combination  with  lime  water.  If  the  stomach  will  not  retain  this,  or  if  it 
gives  distress,  do  not  push  it  further,  but  support  the  strength  by  nutritions  enemata. 
Even  when  the  stomach  is  quiet  and  the  patient  craves  food,  it  will  be  necessary  to 
give  only  liquid  nourishment  for  two  or  three  days,  aud  then  to  allow  nothing  but 
the  simplest  aud  most  digestible  forms  of  solid  foods,  for  there  is  always  danger  of  a 
relapse  from  imprudence  in  diet,  even  in  the  mildest  cases. 

Before  closing  this  article  the  writer  ventures  to  refer  briefly  to  a  method  of  treat- 
ment which  is  still  too  recent  to  permit  of  a  definite  conclusion  as  to  its  value. 

This  was  suggested  by  me  during  my  recent  visit  to  Havana,  and  is  an  attempt  to 
formulate  a  specific  treatment  in  accordance  with  my  present  views  of  the  etiology 
and  pathology  of  the  disease.  The  intensely  acid  condition  of  the  urine  and  of  the 
vomited  matters^  aud  the  fact  that  I  have  usually  found  the  contents  of  the  intestine 
more  or  less  acid,  has  led  me  to  think  that  a  very  decidedly  alkaline  treatment  might 
be  beneficial,  and  in  view  of  the  probability  that  the  specific  infectious  ageut  is  lo- 
cated in  the  alimentary  canal,  I  have  combined  with  the  antacid  selected  an  autisep- 
tic  agent  which  is  kuowii  to  restrict  the  develoi)aient  of  micro-organisms  when  pres- 
ent in  very  minute  quantity. 

The  formula  suggested  was  as  follows : 

R  Bicarbonate  of  soda,  grammes  s,  (150  grains). 
Bichloride  of  mercury,  centigrammes  ii  (3  grain). 
Pure  water,  litre  j,  (1  quart). 
M.  Sig.  50  grammes  (3  tablespoonfuls)  every  hour ;  to  be  given  ice  cold. 

A  letter  recently  received  from  my  friend,  Dr.  D.  M.  Burgess,  sanitary  inspector 
at  Havana,  gives  the  following  account  of  the  results  up  to  the  present  date.  Dr. 
Burgess  says : 

"  Ten  cases  (six  severe  ones)  have  now  been  treated  at  Garcini  by  your  alkaline 
and  bichloride  method  and  all  have  recovered  ;  none  subjected  to  that  method  have 
died.  Three  were  treated  successfully  at  another  hospital  here.  Four  are  to-day  re- 
ceiving the  treatment  at  Garcini,  aud  about  an  equal  number  at  each  of  two  other 
institutions." 

This  article  in  Wood's  Haud-book  of  the  Medical  Sciences  was 
written  soon  after  my  return  from  Cuba,  in  18S8.  Since  that  time  I 
have  received  much  evidence  in  favor  of  the  mode  of  treatment  referred 
to  at  its  close. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER.  85 

The  following  Preliiniuary  Note  iipoQ  a  ^ew  Method  of  Treating- 
Yellow  Fever  was  published  in  the  Therapeutic  Gazette  of  August 
15,  1888 : 

In  view  of  the  recent  aunouuflemeut  that  yellow  fever  has  reappeared  in  Florida, 
and  the  possibility  that  it  may  soou  prevail  as  an  epidemic  in  that  State,  the  writer 
has  decided  to  report  the  favorable  results  recently  attained  in  the  treatment  of  the 
disease  in  Havana  by  a  method  proposed  hy  him,  although  the  number  of  cases  is 
still  comparatively  small. 

My  recent  researches  in  Havana  have  led  me  to  think  it  very  probable  that  in  yellow 
fever,  as  in  cholera,  the  specific  microorganism  causing  the  disease  is  located  in  the 
alimentary  canal.  While  this  is  not  proved,  it  is  demonstrated  that,  as  a  rule,  no 
microorganism  capable  of  development  in  the  culture  media  usually  employed  by 
bacteriologists  is  present  in  the  blood  or  tissues  of  those  recently  dead  from  yellow 
fever.     This  view  naturally  suggests  intestinal  antisepsis  as  a  mode  of  treatment. 

It  is  well  known  that  in  yellow  fever  the  urine  and  the  vomited  matters  are  highly 
acid.  I  have  also  found  the  intestinal  contents  to  have  usually  a  more  or  less  decided 
acid  reaction.  A  microbe,  therefore,  capable  of  multiplying  in  the  stomach  and  in- 
testine in  this  disease,  mnst  be  able  to  grow  in  an  acid  medium.  But  aside  from  this 
theoretical  reason  for  prescribing  alkalies,  the  highly  acid  condition  of  the  secretions 
furnishes  an  indication  for  such  a  treatment,  and  the  writer  has  long  desired  an  ojjpor- 
tunity  to  see  a  thorough  trial  of  a  decidedly  alkaline  treatment. 

These  considerations  induced  me  during  my  recent  visit  to  Havana  to  propose  the 
following  foruiula  : 

^  Sodii  bicarb grammes  x  (gr.  150) ; 

Hydrarg.  chlorid.  corrosiv centigrammes  ii  (1%  gr.) 

Aquai  purse litre  i  (I  qt.) 

M.  Sig.     50  grammes  (about  If  ounces)  every  hour ;  to  be  given  ice  cold. 

This  treatment  was  adopted  by  Dr.  Raphael  Weiss  house  physician  at  the  Garciui 
Hospital,  and  I  have  just  received  from  him  a  re'cord  of  twelve  cases  treated  by  the 
director  of  the  hospital.  Dr.  Francis  Cabera.  and  himself. 

The  complete  temperature  charts  sent  to  me  by  Dr.  Weiss  sustain  the  diagnosis 
in  all  of  these  cases,  and  this  is  confirmed  by  Dr.  Daniel  M.  Burgess,  United  States 
sanitary  inspector,  Marine  Hospital  Service  at  Havana,  who  writes  me : 

"Havana,  July  18,  1888. 

''Mt  Dear  Dr.  Sternberg:  I  send  you  by  this  mail  Dr.  Weiss's  report  of  twelve 
cases  treated  by  the  alkaline  and  bichloride  method.  Although  they  were  all  Span- 
iards, and  were  not  directly  under  my  care,  I  had  sufficient  supervision  of  the  cases 
to  satisfy  me  that  they  were  all  genuine  yellow  fever.  It  will  be  seen  that  they  all 
recovered,  and  I  will  add  that  every  case  so  far  treated  at  the  Garciui  by  that  method 
has  recovered.  While  these  twelve  cases  were  being  treated,  and  a  little  before, 
eight  cases  were  treated  in  the  same  institution  by  other  methods,  and  five  of  the 
eight  died." 

Dr.  Weiss  writes  me  that  in  some  of  the  more  severe  cases  he  increased  the  amount 
of  bichloride  to  5  centigrammes  (three-quarters  of  a  grain)  per  litre.  He  says : 

"Administering  to  the  sick  ihe  bichloride  of  mercury,  according  to  your  directions, 
the  gastric  jihenomena  are  very  much  modified  ;  the  gastric  sediments  appear  later, 
and  in  no  case  have  they  been  entirely  dark.  In  some  cases,  truly  dangerous  on  ac- 
count of  the  state  of  the  patient  in  a  general  sense,  gastric  sediments"  (black  vomit) 
"did  not  appear,  nor  even  nausea.     The  pains  in  the  stomach  were  not  so  severe." 

In  some  of  the  cases  Dr.  Weiss  added  benzoate  of  sodium  to  the  formula  for  its 
laxative  effect,  and  administered  daily  two  enemas  containing  each  a  gramme  (15 
grains)  of  the  phenate  of  sodium. 

Sherry  wine  and  hypodermic  injections  of  ether  were  given  during  the  second  stage, 


86 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVEE. 


when  the  pulse  was  feeble  and  the  condition  of  the  ^latient  seemed  to  call  for  a  stim- 
ulant. 

With  reference  to  tlio  urinary  secretion,  Dr.  Weiss  writes: 

"  The  urine  has  always  been  abundant.  In  some  cases  the  density  lowered,  but 
was  compensated  by  a  large  quantity  of  urine.  Albumen  did  not  appear  in  some  of 
the  cases,  in  others  the  amount  was  small,  and  in  others  it  reached  2  grammes  to 
the  litre.  The  albumen  has  always  disappeared  on  the  second  or  third  day  and  then 
the  fever  ceased." 

Although  Dr.  Weiss  has  sent  me  the  clinical  records  of  only  twelve  cases,  he  says 
in  his  letter : 

"I  have  dealt  with  thirteen  sick  from  the  beginning  of  the  disease  and  all  have 
recovered.  *  *  *  Before  using  this  new  treatment,  during  the  present  season,  we 
had  eight  cases  which  we  treated  from  the  first  day  by  the  old  method  "  (mainly 
symptomatic)  ''and  five  of  the  number  perished." 

This  mode  of  treatment  will,  of*course,  require  a  more  extended  trial  before  the 
results  can  be  fairly  compared  with  those  obtained  by  other  methods.  I  may  remark, 
however,  that  in  similar  cases  treated  by  the  ''expectant"  method  the  mortality 
rarely  falls  below  20  per  cent.,  and  in  hospital  practice  is  often  50  per  cent,  or  even 
more. 

AVhether  the  favorable  results  are  to  be  ascribed  to  the  alkali,  or  to  the  antiseptic 
action  ot  the  bichloride,  can  only  be  determined  by  testing  the  two  remedies  sepa- 
rately ;  but  I  am  very  much  disposed  to  ascribe  the  unusual  absence  of  gastric  dis- 
turbance and  the  abunda,nt  secretion  of  urine  noted  to  the  alkaline  element  of  the 
treatment,  and  it  is  extremely  doubtful  whether  the  bichloride  reaches  the  intestine 
in  sufficient'qnantity  to  exercise  any  decided  antiseptic  eS'ect  in  that  portion  of  the 
alimentary  canal.  The  bicarbonate  should  be  free  from  carbonate  of  sodium,  as  the 
mercuric  chloride  is  decomposed  by  this  salt  and  by  alkalies  generally.  It  is  possible 
that  the  biniodide  might  be  substituted  to  advantage  in  the  formula  above  given. 

In  some  experiments,  made  by  the  writer  several  years  since  to  determine  the  com- 
parative antiseptic  value  of  the  salts  and  oxides  of  mercury,  the  following  results 
were  obtained : 


Biniodide  of  mercury 

Bichloride  of  mercury  . . . 
Protiodide  of  mercury  . . . 
Yellow  oxide  of  mercury  . 
Black  oxide  of  mercury . . 

Calomel 

Blue  mass 


Active. 


1  to  20,  000 
1  to  15,  000 
1  to  10,  000 
1  to  1,000 
1  to        500 


Failed. 


1  to  40,  000 
1  to  20,  000 
]  to  20,  000 
1  to  2,  OCO 
1  to  1,  000 
1  to  100 
1  to   100 


"In  every  case  the  antiseptic  was  carefully  weighed  and  added  to  100  cubic  centi- 
metres of  beef-peptone  solution,  or  of  veal  broth.  A  similar  quantity  of  the  culture 
fluid  was  put  up  as  a  ie?)ioiH  without  the  addition  of  the  antiseptic.  As  the  oxides 
and  iodides  of  mercury  are  insoluble  in  water,  the  bottle  was  repeatedly  shaken  in 
order  to  dissolve  in  the  albuminous  culture  fluid  as  much  of  the  antiseptic  as  pos- 
sible. An  undissolved  remnant  could,  however,  be  recognized  at  the  bottom  of  the 
bottle  after  this  repeated  shaking.  Two'  drops  of  broken  down  beef  stock  were  added 
to  each  bottle  to  cause  speedy  putrefaction  of  the  culture-fluid  in  the  absence  of  a 
sufficiently  potent  inhibition  of  the  developing  power  of  the  bacteria  of  putrefac- 
tion. In  every  case  in  the  comparative  experiment  the  culture  fluid  became  clouded, 
and  had  a  putrefactive  odor  at  the  end  of  24  hours. 

"  The  first  column  in  our  table  shows  the  proportion  in  which  the  culture  fluid  was 
preserved  from  any  appearance  of  decomposition  for  at  least  a  week,  the  duration  of 


ETIOLOGY    AND    PEEVENTION    OF    YELLOW   FEVEE.  87 

tlie  experiment.  lu  the  proportiou  giveu  iu  the  second  column  a  decided  inhibiting 
povrer  was  shown,  except  in  the  case  of  calomel  and  blue  mass,  which,  in  the  pro- 
portion given  (1  to  100),  gave  no  evidence  of  antiseptic  power.  The  other  salts  and 
oxides  in  the  list  prevented  decomposition  for  24  hours  in  the  proportiou  given  in  the 
second  column,  and  ifc  was  not  until  the  second  day  that  the  bacteria  of  putrefac- 
tion commenced  to  form  a  cloud  at  the  upper  surface  of  the  fluid,  which  gradually 
extended  until  the  fluid  had  entirely  broken  down,  usually  by  the  third  or  fourth 
day.  The  bottles  containing  the  biniodide  (I  to  20,000)  and  the  bichloride  (1  to 
15,000)  have  now  been  standing  in  the  laboratory  for  3  weeks,  and  are  as  transparent 
and  free  from  odor  as  the  day  they  were  put  up."* 

The  bichloride,  the  biniodide,  aadthe  oxides  of  mercury  exhibited  a  decided  inhib- 
itory (antiseptic)  effect  upon  the  development  of  the  bacteria  of  putrefaction  in  the 
proportion  given  iu  the  second  column,  and  we  may  use  these  figures  as  a  guide  in 
our  efforts  to  secure  intestinal  antisepsis  by  means  of  these  agents,  although  it  is 
of  course  very  uncertain  how  much  of  the  soluble  mercuric  salt  introduced  into  the 
stomach  reaches  the  intestine  in  au  active  form — probably  very  little,  In  the  formula 
which  I  gave  to  the  physicians  of  the  Garcini  Hospital  the  amount  of  bichloride  pre- 
scribed is  really  only  in  the  proportiou  of  I  to  50,000  parts  of  the  solution.  But  I 
considered  it  advisable  to  commence  the  treatment  with  an  amount  that  was  entirely 
safe,  and  to  increase  the  dose  afterwards,  if  it  was  found  to  be  prudent  and  desirable 
to  do  so.  Dr.  Weiss  lias,  iu  fact,  increased  the  dose  in  several  severe  cases  to  5  centi- 
grammes per  litre— 1  to  20,000.  As  all  of  these  cases  recovered  we  may  infer  that 
when  largely  diluted,  as  in  this  formula,  and  given  in  small  quantities  at  short  inter- 
vals, it  may  be  safely  administeied  in  these  doses;  but,  as  already  intimated,  lam 
rather  disposed  to  attribute  the  favorable  course  of  the  disease  to  the  full  alkaline 
treatment  than  to  any  antiseptic  eftecb  of  the  bichloride  in  the  intestine.  In  the 
stomach,  however,  I  should  expect  a  decided  antiseptic  effect  from  the  medicine  as 
administered  ;  and  perhaps  this  is,  after  all,  what  is  most  needed. 

This  preliminary  note  led  to  an  extended  trial  of  the  proposed  treat- 
ment during  the  epidemics  in  Florida  and  Alabama,  which  occurred 
soon  after  it  was  published.  It  was  also  tested  with  extremely  favor- 
able results  during  the  recent  severe  epidemic  in  Rio  Janeiro,  and  dur- 
ing the  summer  of  1889  has  again  been  put  to  a  practical  test  in 
Havana.  The  results,  so  far  as  reported  to  me,  are  given  below.  I 
quote  .first  from  an  article  published  in  the  Therapeutic  Gazette  of  May 
15,  1889 : 

BICARBONATE    OF    SODIUM    A.ND    BICHLORIDE    OF    MERCURY    IN    THE 
TREATMENT  OF  YELLOW  FEVER. 

By  Geo.  M.  Sternberg,  Major  and  Sure/eon,  77.  S.  Army. 

In  a  "preliminary  note,"  published  in  the  Therapeutic  Gazette  of  August  15,  1888, 
the  writer  gave  the  results  of  a  mode  of  treatment  suggested  by  himself  while  in 
Havana  last  year.  The  cases  referred  to  in  this  note  were  treated  at  the  Garcini 
Hospital  by  Dr.  Raphael  Weiss,  to  whom  I  am  indebted  for  clinical  histories  of 
twelve  successive  cases  treated  without  a  single  fatal  result. 

The  object  of  the  present  paper  is  to  record  the  results  of  a  more  extended  trial 
of  the  same  treatment  during  the  recent  epidemics  at  Decatur,  Ala.,  and  at  Jack- 
sonville, Fla. 

Upon  my  arrival  in  Decatur,  in  the  early  part  of  October  last,  I  found  that  yellow 

*From  a  report  of  the  committee  on  disinfectants  of  the  American  Public  Health 
Association,  1885. 


88 


ETIOLOGY    AND    PREVENTION    OF   YELLOW    FEVER. 


fever  of  a  most  malignaut  type  was  prevailing,  and  that  the  mortality  had  been 
very  great  even  under  tlie  most  favorable  conditions  as  to  nursing  and  surroundings. 
This  is  shown  by  the  fact  that  out  often  physicians  practicing  in  the  infected  area, 
nine  had  yellow  fever  and  five  died.  The  one  who  escaped,  Dr.  B.  F.  Cross,  had  suf- 
fered an  attack  during  a  previous  epidemic  in  the  same  place  (1878).  Soon  after  my 
arrival  I  called  attention  to  the  allialine  and  bichloride  treatment,  and,  in  view  of 
the  verj'  unsatisfactory  results  which  had  been  obtained  by  other  methods,  the  physi- 
cians remaining  on  duty,  two  of  whom  were  recent  convalescents,  one  after  another 
adopted  the  treatment.  Since  the  termination  of  the  epidemic  they  have  kindly 
given  me  a  statement  of  the  results  obtained,  and  more  or  less  complete  clinical  his- 
tories of  their  cases. 

The  formula  originally  prescribed  by  me  as  published  in  my  preliminary  note  in 
the  Therapeutic  Gazette  was  adhered  to.     This  is  as  follows  :    ■ 

[J;.  Sodii  bicarb.,  gi-ammes  x  (grs.  150). 

Hydrarg.  chloridi  corrosiv.,  centigrammes  ii  (ro  gc-) 

Aquaj  puraj,  litre  i  (1  quart).     M. 

Sig. :  50  grammes  (about  If  ounces)  every  hour ;  to  he  given  ice  cold. 

EesuHs  of  ireatmeut  hi  Decatur. 


Treated  by- 


Dr.  B.  F.  Cross 

Dr.  E.  J.  Couyngton 
Dr.  E.  M.  Littlejohn 
Dr.  W.  C.  Buckley  . 

Total 


Whites. 


M. 


Died. 


Colored. 


M. 


F.      Died. 


I  have  excluded  from  the  above  tabular  statement  two  cases  treated  by  Dr.  Cross, 
in  which  the  treatment  was  not  commenced  at  the  outset  of  the  attack.  One  of 
these,  a  white  male,  terminated  favorably;  the  other,  a  white  female,  resulted 
fatally.  Dr.  Cross  remarks,  with  reference  to  the  last-mentioned  case:  "  She  was 
taken  sick  on  the  29th  of  September  and  died  November  10;  was  not  jiut  on  the  Stern- 
berg treatment  until  the  latter  part  of  her  illness." 

The  two  fatal  cases  in  the  practice  of  Dr.  Cross  were:  No.  1,  Mr.  J.;  aged  about 
30;  taken  sick  October  18 ;  died  October  23,  after  suppression  of  urine  and  black 
vomit.  No.  2,  Mrs.  D.,  a  feeble  woman  of  53  or  60,  who  had  recently  lost  her  hus- 
band from  the  same  disease. 

The  fatal  case  in  Dr.  Couyngfcon's  practice  was  :  Captain  K.,  "  aged  about 50 years; 
a  large,  plethoric  man,  rather  a  heavy  drinker  ;  had  been  in  the  habit  of  drinking 
whisky  for  30  years."  This  patient  had  suppression  of  urine  on  the  fourth  daj'  of 
sickness. 

The  fatal  case  treated  by  Dr.  Bnckley  was:  Mr.  B.,  aged  33.  "The  patient  had  a 
severe  case  of  yellow  fever,  but  was  doing  well,  considering  the  severity  of  his  case, 
until  the  morning  of  the  seventh  day,  when  he  was  found  much  worse.  *  *  *  It 
was  ascertained  that  the  family  gave  him  a  hearty  meal  on  the  sixth  day — the  one 
previous  to  his  becoming  worse." 

Through  the  kindness  of  Dr.  Jerome  Cochran,  State  health  officer,  I  have  received 
the  following  official  statement  of  the  number  of  cases  and  deaths  in  the  Decatur 
epidejnic  : 

Whites :  Colored : 

Cases 97  Cases 57 

Deaths 30  Deaths 5 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  89 

This  gives  xis  a  general  mortality  of  22.72  per  cent.,  aud  a  mortality  amoug  the 
whites  alone  of  30.92  per  cent. 

Reference  to  the  above  table  will  show  that  in  a  total  of  64  8jp,se8  treated  by  the 
alkaline  and  bichloride  method  the  mortality  was  only  6.45  per  cent.,  aud  that  the 
mortality  amoug  the  whites,  considered  separately,  was  12.5  per  cent. 

A  just  comparison,  hovrever,  requires  that  we  shall  deduct  the  number  treated  by 
tlio  method  under  investigation  from  the  total  number  of  cases  occurring  during  the 
epidemic.  Tbis  leaves  us  65  whites  with  26  deaths,  and  25  colored  with  5  deaths 
treated  by  other  methods;  aud  gives  a  mortality  of  40  per  cent,  among  the  white 
and  20  per  cent,  among  the  colored  population ;  whereas  under  the  alkaline  and 
bichloride  treatment  not  a  single  death  occurred  out  of  32  cases  among  the  colored 
jjopulation — many  of  the  cases  were  bright  mulattoes — and  the  mortality  among  the 
whites  was  reduced  to  12.5  per  cent. 

RESULTS  OF   TREATMENT  IX  JACKSONVILLE,    FLA. 

My  "preliminary  note  "  in  the  Therapeutic  Gazette  was  brought  to  the  attention 
of  some  of  the  physicians  iu  Jacksonville  during  the  recent  epidemic,  and  I  am  in- 
formed that  a  number  of  them  employed  the  treatment  referred  to,  and  that  it 
gave  general  satisfaction  to  those  who  adopted  it.  I  have  as  yet  only  obtained  a  de- 
tailed report  from  two  physicians,  but  as  these  reports  include  a  considerable  number 
of  cases  treated  in  the  Sand  Hills  Hospital  by  Dr.  Sollace  Mitchell,  and  in  private 
practice  by  Dr.  A.  J.  Wakefield,  they  may  be  taken  as  fairly  representing  the  gen- 
eral results  obtained  by  this  method  of  treatment  during  the  Jacksonville  epidemic. 

Dr.  Mitchell  writes  me  as  follows: 

"  Jacksoisville,  Fla.,  Sejytemher  9,  18S9. 
"G.  M.  Sternberg,  M.  D., 

"  Baltimore,  Md.  : 

"My  Dear  Doctor  :  I  send  you  to-day  a  list  of  all  cases  treated  upon  the  bichloride 
and  alkaline  treatment ;  also  those  upon  the  triturated  bichloride  without  the  alkali. 
I  confess  my  surprise  at  the  great  diiference  in  mortality.  I  knew  that  my  results  with 
the  alkali  were  far  better  than  without  it,  but  did  not  realize  the  great  difference 
until  I  made  out  these  lists  for  you.  Some  of  the  ages  have  been  approximated,  be- 
cause the  book  containing  the  ages,  reception,  etc.,  of  many  has  been  lost  or  mislaid, 
I  treated  in  all  216  cases.  I  did  not  begin  the  use  of  the  bichloride  until  I  had  treated 
some  35  or  40  by  other  methods,  and  when  the  bichloride  was  begun  only  every 
fourth  patient  was  put  upon  it,  then  every  other  patient,  and  towards  the  last  almost 
all  patients  were  put  upon  it  (i.  e.,the  alkaline  and  bichloride  treatment.  G.  M.  S.) 
Cases  were  chosen  by  rotation  as  they  came  iu,  different  treatment  being  used  iu 
different  wards.  The  bichloride  aud  alkali  gave  the  best  results  by  all  odds. 
"Most  sincerely,  yours, 

"Sollace  Mitchell." 

The  lists  transmitted  by  Dr.  Mitchell  give  the  name,  age,  color,  sex,  and  result, 
with  a  remark  as  to  the  severity  of  each  case. 

The  list  of  those  treated  by  the  alkaline  and  bichloride  method  includes  106  cases, 
with  5  deaths,  a  mortality  of  4.7  per  cent. 

Seventy-nine  of  these  cases  and  all  of  the  deaths  were  whites,  a  mortality  of  6.3  per 
cent.    Twenty-seven  cases  were  colored,  with  no  deaths. 

Of  the  whites^  73  were  males  and  6  females.  The  deaths  all  occurred  among  the 
white  males,  and  the  mortality  among  this  class,  considered, separately,  were  6.8  per 
cent.  This  is  certainly  a  very  unusual  result,  aud  brings  out  in  a  very  striking  man- 
ner the  value  of  this  mode  of  treatment.  Yellow  fever  is  well  known  to  be  especially 
fatal  among  adult  males,  and  in  hospital  practice  a  mortality  of  less  than  25  per  cent, 
amoug  this  class  of  cases  is  exceptional. 

The  mortality  lists  published  iu  the  newspapers  during  the  Jacksonville  epidemic 
gave  the  impression  that  the  epidemic  was  of  an  uuusually  mild  character.     But  it 


90  ETIOLOGY    AND    PEEVENTION    OF    YELLOW    FEVEE. 

iimst  be  reuiciubered  that  tlieso  lists  related  to  the  poj)ulatiou  generally,  and  included 
a  very  large  proportion  of  the  colored  race,  who  remained  in  the  infected  citj^  while 
a  large  share  of  the  white  i^opulation  left  it  upon  the  outbreak  of  the  epidemic. 
Now,  the  mortality  from  this  disease  among  negroes  is  always  small,  and  is  estimated 
by  Dr.  Mitchell  not  to  have  been  over  2  per  cent,  in  the  Jacksonville  epidemic.  Yet 
the  general  mortality,  as  shown  by  the  daily  reports  published  in  the  newspapers, 
was  in  the  vicinity  of  10  per  cent.  Dr.  Mitchell  estimates  the  mortality  among  the 
white  population,  considered  separately,  as  from  22  to  25  per  cent.,  but  has  not  yet 
been  able  to  give  me  the  exact  figures.  This  estimate  includes  both  sexes  and  all 
ages,  and  if  adult  males  were  considered  separately  it  would  no  doubt  be  considerably 
more  than  this.  With  two  or  three  exceptions  the  79  whites  included  in  Dr.  Mitch- 
ell's list  were  adults;  one  only  was  a  child  of  8  years;  10  were  between  1.5  and  20 
years  ;  25  from  20  to  30  ;  29  from  30  to  40 ;  11  from  40  to  50,  and  3  from  50  to  60. 

The  cases  are  classified  by  Dr.  Mitchell  as  to  severity  as  follows:  "Mild,"  46; 
"severe,"  19;  "very  severe,"  14.  It  must  be  remembered  that  the  treatment  was 
commenced  at  the  outset,  and  the  mildness  of  the  attack  in  those  cases  classified  as 
"mild"  may  have  been  due  to  some  extent  to  the  favorable  influence  of  the  medicine 
administered.  Indeed,  the  general  result  indicates  that  such  was  the  fact.  It  is  well 
known  to  those  physicians  who  have  had  an  extended  experience  in  the  treatment  of 
yellow  fever  that  many  cases  which  appear  to  be  mild  at  the  outset  in  the  end  ter- 
minate fatally,  and  especially  so  in  adult  males,  among  whom  the  tendency  to  sup- 
pression of  urine  seems  greater  than  in  tlaecase  of  females  and  childi'en. 

One  of  the  principal  objects  which  I  had  in  view  in  prescribing  full  doses  of  bicar- 
bonate of  sotlium  at  regular  intervals  was  to  neutralize  the  very  acid  condition  of 
the  urine,  in  the  hope  that  it  might  be  secreted  more  abundantly  and  with  less  injury 
to  the  renal  parenchyma.  The  results  attained  seem  to  indicate  that  such  Is  the 
case,  and  that  the  favorable  action  of  the  medicine  is  largely  due  to  this  fact. 

Dr.  Weiss,  in  transmitting  the  clinical  notes  of  twelve  successive  cases  treated  in 
the  Garcini  Hospital,  in  Havana,  in  1838,  without  a  death,  says : 

•■'The  urine  has  always  been  abundant.  In  some  cases  the  density  was  lowered, 
but  was  compensated  by  a  large  quantity  of  urine.  Albumen  did  not  appeai*  in  some 
of  the  cases,  in  others  the  amount  was  small,  and  in  others  it  reached  2  grammes  to 
the  litre.  The  albumen  has  always  disappeared  on  the  second  or  third  day,  and  then 
the  fever  ceased." 

Dr.  Conyngton,  of  Decatur,  remarks : 

"One  point  of  special  note  was  that  patients  on  this  treatment  in  my  hands  never 
had  any  symptoms  of  suppression  of  urine,  but  rather  the  quantity  was  increased; 
while,  on  the  other  hand,  in  patients  treated  by  the  expectant  plan,  with  diuretics, 
the  urine  was  scanty,  and  those  that  died  (3  in  number)  died  of  suppression." 

Dr.  Sollace  Mitchell,  in  a  letter  dated  February  1,  speaks  of  the  "marked  effect  of 
the  treatment"  in  diminishing  the  albumen  and  preventing  in  a  great  measure  su^i- 
pression  of  urine. 

Dr.  A.  J.  Wakefield,  of  Jacksonville,  has  given  me  a  list  of  89  cases  treated  by 
himself  during  the  recent  epidemic  in  that  city.  Of  these  cases  75  were  white  and 
14  colored.  Five  deaths  occurred  among  the  whites — a  mortality  of  6.6  per  cent. 
Thirty-nine  of  the  white  cases  were  males  and  36  females  ;  41  of  the  cases  are  classed 
as  severe  and  48  as  mild.  One  of  the  fatal  cases  is  said  to  haVe  been  a  consumptive; 
1  to  have  been  convalescent  and  to  have  died  from  imprudence;  in  another  the  re- 
mark is  made  "  bad  nursing  and  imprudence";  another,  "unfavorable  surroundings." 

BESULTS   OF   TREATMENT  AT   KIO   DE   .TAXEIRO. 

My  friend  Dr.  Cleary,  an  American  physician  practicing  at  Rio  de  Janeiro,  in  a  letter 
dated  December  13,  1888,  gives  me  an  account  of  4  cases  treated  by  this  method  ;  3 
made  a  good  recovery  and  1  died.  The  fatal  case  assumed  a  severe  form  from  the  out- 
set, and  was  attended  with  hemorrhage  from  the  vagina.    Black  vomit  and  suppression 


ETIOLOGY    ATTO    PREVENTION    OF    YELLOW    FEVER.  91 

of  urine  occurred  ou  the  fourth  tlay.  Dr.  Cleary  thinks  that  in  this  case  no  treatnieut 
woukl  have  been  of  any  avail,  and  says,  in  conclusion  :  "  Should  any  new  cases  present 
themselves  to  me  I  shall  continue  using  your  method,  as  I  believe  in  it." 

Since  the  above  was  written  I  have  received  a  letter  from  Dr.  Cleary,  in  which  he 
says  : 

"In  all  I  have  treated  34  cases  of  yellow  fever,  all  of  them  genuine,  but  as  about 
one-half  did  not  present  albumen  in. the  urine  nor  "blade  vomit"  they  might  be  con- 
tested, yet  thej"  all  began  with  sudden  chilliness,  then  excessive  temperature,  mostly 
■with  dry  skin  (temperature  39.9°  to  40.5°),  which  lasted  from  12  to  72  hours,  abating 
somewhat;  tongue  whitey-yellowish,  skin  yellow,  great  hypenemia  of  the  thoracic 
integument,  some  diminution  of  the  urine,  gastric  uneasiness,  and  vomiting. 

"In  my  opinion  and  that  of  an  experienced  Brazilian  physician  they  were  un- 
doubted cases  of  yellow  fever.  Of  these  34  cases  I  lost  only  I — that  is  the  one  I 
wrote  j'on  about — and  in  every  case  I  used  your  fornaula  steadily  throughout." 

I  have  recently  received  a  clipping  from  the  Journal  of  Commerce  of  Rio  de  Janeiro, 
containing  a  note  from  Dr.  Rocha  Faria,  inspector  of  hygiene,  in  which  the  formula 
prescribed  by  me  is  given  and  strongly  recommended.     Dr.  Faria  says  : 

"Some  physicians  who  during  the  present  ejiidemic  have  followed  this  treatment 
have  obtained  magnificent  results.  " 

The  question  arises  as  to  whether  the  favorable  results  which  have  thus  far  attended 
this  mode  of  treatment  are  due  to  the  alkaline  element  of  the  treatment,  or  to  the 
antiseptic  element,  or  to  the  combined  action  of  the  two  ingredients. 

My  principal  object  in  suggesting  the  formula  was  to  test  a  decidedly  alkaline 
treatment  from  the  outset  of  the  attack,  with  a  view  to  relieving  the  gastric  distress 
and  acid  vomiting  which  is  a  prominent  feature  in  cases  treated  by  the  expectaut 
method,  and  also  to  render  the  highly^  acid  urine  neutral  or  slightly  alkaline,  in  the 
hope  that  the  secretion  would  be  more  abundant  and  the  tendency  to  suppression 
diminished.  The  treatment  api^ears  to  meet  these  important  indications;  and,  with- 
out in  any  sense  being  "specific,"  to  save  life  by  preventing  those  structural  changes 
which  give  rise  to  passive  hemorrhage  from  the  stoqiach  and  suppression  of  urine — 
two  symptoms  which  present  themselves  in  a  majority  of  the  fatal  cases. 

Bichloride  of  mercury  in  a  comparatively  small  amount  was  added  to  the  formula, 
not  with  the  idea  that  it  would  to  any  extent  destroy  pathogenic  microorganisms  in 
the  intestine,  but  as  an  antiseptic,  which  might  be  useful  in  preventing  fermentative 
changes  in  the  stomach,  which  would  perhaps  be  favored  by  the  free  administration 
of  an  alkali.  The  idea  has  also  occurred  to  me  that  the  specific  germ  may  possibly 
find  a  suitable  nidus  in  the  acid  secretions  of  the  stomach,  and  in  this  case  the  admin- 
istration of  an  antiseptic  in  combination  with  an  alkali  would  be  the  most  rational 
treatment.  Still,  I  have  not  given  much  weight  to  this  idea.  In  my  "  preliminary 
note"  I  say  :  "I  am  rather  disposed  to  attribute  the  favorable  course  of  the  disease  to 
the  full  alkaline  treatment  than  to  any  antiseptic  effect  of  the  bichloride  in  the  intes- 
tine. In  the  stomach,  however,  I  should  expect  a  decided  antiseptic  effect  from  the 
medicine  as  administered,  and  perhaps  this  is,  after  all,  what  is  most  needed."  I 
insist  upon  this  point,  because  the  treatment  has  frequently  beec  referred  to  by  those 
who  have  used  it  as  the  "  bichloride  treatment."  From  my  point  of  view  it  is  essen- 
tially an  alkaline  treatment,  with  the  addition  of  a  certain  amount  of  the  bichloride 
of  mercury  as  an  adjuvant  to  meet  certain  indications,  but  which  is  not  adminis- 
tered with  the  expectation  that,  by  virtue  of  its  germicide  power,  it  may  prove  a 
specific  in  this  disease. 

Bichloride  of  mercury  has,  however,  during  the  past  year  been  administered  in 
considerably  larger  doses  than  I  have  prescribed  in  the  above  formula,  with  the  ex- 
press purpose  of  destroying  pathogenic  microorganisms  in  the  intestine.  This  treat- 
ment was  proposed  by  Dr.  Paul  Gibier  during  his  stay  in  Havana  last  year,  and  has 
been  fairly  tested  by  Dr.  Vincent  de  la  Guardia  in  his  wards  in  the  charity  hospital 
of  that  city. 


92  ETIOLOGY    AND    PEEVENTION    OF    YELLOW    FEVER. 

The  idea  that  the  specific  iufectious  ageut  of  yellow  fever  may,  as  in  cholera,  have 
its  habitat  iu  the  aliiueutary  caual,  has  bceu  forced  upon  the  writer  by  his  failure  to 
find,  it  iu  the  blood  and  tissues  of  those  suffering  from  the  disease.  Dr.  Gibior  has 
been  led  to  a  similar  iufereuce,  and  has  even  claimed  the  discovery  of  a  bacillus 
which,  as  we  think  upou  insuf3Qcieut  evidence,  he  supposes  to  be  the  specific  infec- 
tious ageut  in  question.  The  treatment  proposed  by  him  is  based  upon  this  idea, 
and  consists  in  the  free  administration  of  ijurgatives  for  the  purpose  of  clearing  the 
pathogenic  microbes  out  of  the  intestine,  and  of  bichloride  of  mercury  in  large  doses 
for  its  geruiicide  eifect.  So  far  as  the  j)wi'g«itiou  is  concerned,  experienced  physicians 
iuthe  yellow-fever  zone  generally  agree  that  it  is  important  to  clear  out  the  bowels 
with  a  brisk  purge  at  the  outset  of  the  attack;  but  it  is  also  established  by  expe- 
rience that  active  medication  of  this  kind  after  the  first  aud  second  day  of  an  attack 
is  likely  to  do  more  harm  than  good,  and,  in  fact,  is  a  dangerous  procedure. 

I  quote  from  the  paper  of  Dr.  de  la  Guardia,  published  in  the  Cronica  Medico- 
Quirnrgica,  of  Havana,  as  follows  : 

"We  have  been  constant  in  giving  the  patients  the  series  of  purges  recommended; 
tbe  first  day  a  saline  cathartic,  45  grammes  of  sulphate  of  sodium  ;  the  second  day, 
45  grammes  of  castor  oil  in  emulsion,  with  an  equal  quantity  of  sirup  ;  and,  finally, 
on  the  third  day,  I  gramme  of  calomel,  to  which  we  added  1  gramme  of  jalap  to  make 
it  more  active,  given  in  two  doses  at  an  interval  of  one  hour.  The  saline  purge  was 
frequently  rejected  by  vomiting,  and  this  also  happened  sometimes  with  the  castor 
oil ;  not  so  with  the  calomel,  which  is  generally  tolerated.  During  the  period  of  large 
evacuations  we  invariably  made  use  of  the  mercurial  medication  ;  using  a  draft 
composed  of  5  centigrammes  of  bichloride  of  mercury,  30  granmies  of  brandy,  and  120 
grammes  of  sweetened  water.  Some  patients  rejected  this  by  vomiting  immediately 
after  taking  it.  The  patients  were  made  to  take  this  until  the  seventh,  or,  in  some 
cases,  the  eighth  day  ;  at  this  time  the  favorable  or  unfavorable  result  was  decided. 
During  his  illness  the  patient  was  given  a  large  quantity  of  liquid  iu  the  form  of 
chlorhydric  lemonade  (2  to  1,000)  iced.  This  was  well  retained  by  the  stomach.  Milk 
was  the  only  food  allowed,  generally  iced.  In  some  of  the  most  severe  cases  the 
purgatives  were  again  commenced.  Certain  symptoms  were  treated  by  special 
measures,  in  accordance  with  general  principles.  Vomiting,  for  example,  was  treated 
by  the  application  of  a  blister  to  the  epigastrium,  and  the  patient  was  allowed  to 
swallow  small  pieces  of  ice,  Eivier's  draft,  etc.  Hemorrhage  was  treated  with 
ergot,  and  adynamia  by  tonics.  The  bichloride  of  mercury  has  rarely  given  rise  to 
stomatitis,  and  when  this  has  hap]Dened  it  has  been  mild  in  character,  and  has  been 
rapidly  cured  with  simple  emollient  washes  or  with  chlorate  of  potassium. 

"Thirty-seven  cases  were  submitted  to  the  mercurial  treatment,  all  of  them  typical 
cases  of  yellow  fever,  in  St.  Margaret's  ward  of  the  civil  hospital.  Of  these,  22  recov- 
ered and  15  died.  Tliis  gives  a  mortality  of  40  per  cent.,  which  is  about  the  average 
mortality  from  this  disease  in  Havana;  a  little  more  or  less,  but  rather  more. 

"It  will  be  seen  that  the  result  of  our  scrupulous  investigation  up  to  the  present 
time  has  been,  if  not  disadvantageous,  at  least  without  any  advantage  to  the  patients 
treated." 

In  a  letter  from  Dr.  Sollace  Mitchell,  from  which  I  have  already  quoted,  he  says  : 
"Dr.  Gibier  claims  to  have  suggested  the  use  of  bichloride  internally  some  weeks 
prior  to  yourself.  He  says  that  he  suggested  one-tenth  grain  every  hour.  But  as  I 
experimented  with  doses  from  one-twentieth  to  one-sixtieth,  and  found  that  in  6 
cases  when  one-twentieth  was  used  severe  cramps  and  diarrhea  followed  in  from  6  to 
18  hours,  I  doubt  very  much  if  a  patient  could  bear  one-tenth  grain  with  advantage 
to  himself." 

Dr.  Mitchell  has  given  me  a  list  of  40  cases  treated  by  the  bichloride  alone;  32  of 
these  were  whites  and  8  colored;  9  of  the  whites  died,  a  mortality  of  28  per  cent.; 
whereas  the  mortality  among  the  same  class  of  patients  treated  by  the  alkaline  and 
bichloride  method  was  only  6.3  per  cent. 


ETIOLOGY    AND    PKEVENTION    OF    YELLOW    FEVER.  93 

Dr.  Mitchell  has  given  the  followiBg  summary  statement  of  the  results  obtained 
by  the  two  methods  of  treatment: 

"One  hundred  and  six  cases,  bichloride  and  alkaline  treatment,  with  5  deaths,  and 
1  recovery  from  black  vomit;  40  cases  bichloride  treatment,  with  9  deaths  and  5  re- 
coveries from  black  vomit." 

In  Dr.  Mitchell's  letter  to  me  I  read  the  sentence  last  quoted,  "and  25  recoveries 
from  black  vomit,"  and  it  was  so  published.  This  large  proportion  of  cases  with 
black  vomit  led  me  to  infer  that  the  bichloride  as  administered  had  a  tendency  to 
produce  passive  hemorrhages  from  the  stomach.  But  Dr.  Mitchell  has  since  informed 
me  that  this  sentence  should  read  "and  5  recoveries  from  black  vomit."  My  re- 
marks on  this  point  have  therefore  no  foundation. 

I  have  but  a  single  series  of  cases  to  report  in  which  the  bicarbonate  of  sodium 
was  administered  alone.  These  cases  were  treated  at  the  "Qninta  La  Pnrissma  Con- 
cepcion"  by  Dr.  Duran.  The  formula  used  was  :  Bicarbonate  of  sodium,  6  grammes; 
sweetened  water*,  250  grammes.  Of  this  mixtures  2  tablespoonsful  were  administered 
every  2  hours,  or  about  9  grammes  (135  grammes)  of  the  bicarbonate  of  sodium  in  the 
24  hours.  I  have  no  information  as  to  the  character  of  the  cases  or  as  to  how  long 
the  treatment  was  continued.  It  often  happens  in  the  private  hospitals  of  Havana 
that  the  patients,  when  brought  to  the  hospital,  have  already  been  sick  for  several 
days,  and  the  mortality  is  greatly  influenced  by  this  fact.  In  all,  30  cases  are  re- 
ported as  having  been  treated  by  this  solution,  with  8  deaths,  a  mortality  of  26.G  per 
cent.  At  the  same  time  11  cases  were  treated  by  the  "  antiseptic  method,"  with  6 
deaths,  a  mortality  of  54.5  per  cent.  The  antiseptic  administered  was  biniodide  of 
mercury  2  centigrammes,  in  250  centigrammes  of  sweetened  water — two  tablespoons- 
ful every  2  hours. 

It  will  be  noted  that  the  amount  of  bicarbonate  of  sodium  in  the  formula  used  at 
the  Quinta  la  Pnrissima  Coucepcion  was  less  than  in  my  original  prescrij)tion.  I  am 
disposed  to  think  that  it  would  have  been  better  to  increase  the  dose.  This  was 
done  by  Dr.  Sollace  Mitchell  in  the  Sand  Hills  Hospital  at  Jacksonville,  and  his 
results  fully  justify  his  judgment  in  this  regard.  In  making  my  formula  at  first,  in 
the  absence  of  any  clinical  experience  in  this  disease  with  the  special  remedies  I 
proposed  to  use,  1  felt  that  it  would  be  wise  to  keep  within  the  bounds  of  perfect 
safety,  but  Dr.  Mitchel  has  shown  that  the  doses  of  bicarbonate  of  sodium  may  be 
considerably  increased  not  only  with  safetj^,  but  with  excellent  results.  He  says, 
"  The  formula  that  I  finally  adopted  was : 

1^    Sodii  bicarb.,  grs.  x  to  Ix; 
Hyd.  chlor.  corros.,  gr.  1-30; 
Aqua3  pur£e,  3  iv.     M. 
"Give,  ice  cold,  every  hour  during  the  day  and  every  2  hours  at  night." 
This,  taking  the  minimum  amount,  10  grains,   would  make  3  drams   of  bicar- 
bonate of  sodium  and  six-tenths  of  a  grain  of  bichloride  of  mercury  in  the  24  hours. 
I  prefer  to  prescribe  a  sufficient  quantity  for  the  24  hours  and  to  give  the  medicines 
more  largely  diluted.     I  noticed  at  Decatur  that  the  patients  not  only  took  the 
mixture  as  originally  prescribed  by  me  without  objection,  but  that  they  looked 
forward  to  the  time  when  the  medicine  was  to  be  administered,  as  they  found  the 
ice-cold  drink  refreshing.     And  as  vomiting  has  not,  in  my  observation,  been  induced, 
but  on  the  other  hand,  gastric  irritability  has  been  allayed,  I  can  see  no  objection  to 
giving  the  hourly  dose  in  1^  to  2  fluid  ounces  of  water.    Indeed,  I  think  that  the 
taking  of  a  considerable  amount  of  fluid,  if  it  is  promptly  absorbed  by  the  stomach,  is 
rather  beneficial  than  otherwise.     My  original  prescription  contained  an  amount  of 
water,  1  litre,  which  in  my  judgment  the  patient  might  be  permitted  to  drink  in 
divided  doses  in  the  course  of  the  24  hours.     Under  certain  circumstances,  of  course, 
this  might  be  increased  by  giving  small  draughts  of  cold  water  or  bits  of  ice  in  the  in- 
tervals between  the  administration  of  the  medicine.     But  excess  in  this  direction  will 
often  induce  vomiting,  and  I  have  desired  to  avail  myself  of  the  advantage  of  a- 


94  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVEK. 

formula  which  contains  a  proper  amount  of  water,  to  be  administered  at  short  inter- 
vals, instead  of  leaving  the  administration  of  thisllnid  to  the  judgment  of  the  nurse, 
or  the  desires  of  the  patient.  In  this  way,  also,  the  whole  treatment  becomes  ex- 
tremely simple  and  is  easily  carried  out,  no  small  advantage  for  the  busy  practitioner 
during  the  prevalence  of  an  epidemic. 

In  view  of  these  considerations  and  of  the  experience  of  Dr.  Sollace  Mitchell  with 
increased  doses  of  the  two  ingredients  contained  in  my  original  formula,  I  would 
suggest  for  further  trial  the  following: 

li     Sodii  bicarb.,  grammes  xvi  (3  iv)- 

Hyd.  chlor.  corros.,  centigrammes  iii  (gr.  i). 
Aqua3  PuriB,  litre  1  (1  quart).     M. 
Sig:  50  grammes  (about  1|  ounces)  every  hour;  to  be  given  ice  cold. 

Naturally  the  amount  given  should  vary  according  to  the  age  of  the  patient,  and 
perhaps,  also,  with  reference  to  the  severity  of  the  case.  Thus  a  mild  case  might 
have  two  tablespoonfuls  every  hour  during  the  day  and  every  two  hours  at  night, 
while  a  case,  which  at  the  outset  appeared  to  be  of  a  grave  character,  might  take  2 
fluid  ounces  of  the  mixture  every  hour  day  and  night.  Experience  may  show  that  the 
dose  of  bicarbonate  of  sodium  may  be  still  further  increased  in  severe  cases  with  benelit 
to  the  I'atieut,  but  I  doubt,  in  view  of  the  evidence  above  recorded,  whether  there  would 
be  any  advantage  lit  increasing  the  dose  of  mercuric  chloride.  It  would  be  a  mistake 
to  attempt  to  substitute  a  potassium  salt  for  the  bicarbonate  of  sodium  in  the  above 
formula.  The  mercuric  chloride,  which  remains  in  solution  in  presence  of  sodium 
bicarbonate  in  the  proportions  prescribed,  would  be  precipitated  by  potassium  car- 
bonate. Moreover,  the  potassium  salts  are  directly  contraindicated  in  a  disease  in 
which  there  is  a  great  tendency  to  suppression  of  urine,  and  ur;cmic  poisoning.  The 
experiments  of  Zelz  and  Eitter,  and  of  Bouchard,  show  that  in  ur;emia  the  toxic 
symptoms  are  largely  due  to  the  retention  of  potassium  salts  rather  than  to  urea. 
Bouchard  especially,  as  a  result  of  his  extended  experiments,  insists  upon  "  the  great 
importance  of  limiting  potassium  salts,  both  in  food  and  medicine,  in  the  treatment  of 
uraemia." 

I  may  add  that  a  rather  extended  trial  of  carbonate  of  potassium  in  full  doses, 
made  by  one  of  the  physicians  of  Decatur  during  the  recent  epidemic,  was  attended 
with  a  high  rate  of  mortality,  and  that  the  physician  referred  to  himself  fell  a  victim 
to  the  disease,  although  his  case  at  the  outset  appeared  to  be  rather  a  mild  one. 
How  far  the  treatment  influenced  the  result  it  is,  of  course,  impossible  to  determine, 
but  suppression  of  urine  and  black  vomit  occurred  on  the  fourth  day,  and  death 
quickly  followed. 

Havanna,  April  6,  1889. 

During  the  past  summer  (1889),  Dr.  D.  M.  Burgess,  Uuitecl  States 
sanitary  inspector  at  Havana,  has  treated  all  of  his  yellow-fever  cases 
with  the  alkaline  and  bichloride  method.  He  reports  as  follows  in  a 
letter  dated  Havana,  December  29,  1889: 

I  have  to  report  that  I  have  had  this  season  up  to  date  25  private  cases  of  yellow 
fever;  they  were  all  given  "  Sternberg's  treatment,"  and  while  many  of  them  were 
severe  cases,  all  recovered. 

The  results  of  the  trial  of  this  treatment,  made  in  the  Charity  Hospital 
at  Havana  by  Dr.  Yincente  de  la  Guardia  and  Dr.  Emilio  Martinez 
during  the  past  summer,  are  given  in  a  paper  by  the  last-named 
gentleman,  published  in  the  "Eevista  de  Ciencias  Medicas,"  of  Sep- 
tember 5,  1889.  This  report  is  especially  valuable  because  Dr.  La 
Guardia  has  bad  an  extended  experience  in  the  same  hospital  with 
similar  cases  occurring  during  preceding  years,  and  because  he  had 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


95 


made  in  the  summer  of  1888  a  careful  test  of  the  method  of  treatment 
proposed  by  Dr.  Paul  Gibier,  which  consisted  in  the  administration  of 
purgatives,  and  of  full  doses  of  mercuric  chloride.  His  report,  which 
was  unfavorable  to  this  mode  of  treatment,  is  referred  to  in  m^'  last 
paper  in  the  Therapeutic  Gazette,  quoted  above. 
Dr.  Martinez  says  in  the  paper  referred  to  : 

Associated  with  Dr.  D.  Vincente  de  la  Gnardia,  physician  to  the  Mercedes  Hospital, 
and  authorized  by  the  director  of  this  institution,  it  was  resolved  to  submit  the  alka- 
line and  mercurial  treatment  of  Dr.  Stei'nberg,  which  had  given  such  excellent  re- 
sults in  the  recent  epidemic  at  Decatur,  in  the  United  States,  to  an  extensive  trial. 

The  plan  followed,  in  general  terms  was  as  follows :  Upon  the  admission  of  the 
patient  a  purgative  was  ordered,  if  he  had  not  passed  the  third  day,  in  which  case 
we  prescribed  a  purgative  enema.  From  the  first  we  commenced  to  administer  the 
following  formula: 

1^     Bicarbonate  of  soda,  16  grammes. 

Bichloride  of  mercury,  2  centigrammes. 
Water,  1  litre. 
Forty-five  grammes  to  be  given  ice  cold  every  hour,  day  and  night. 

For  the  first  5  or  6  days  no  food  was  given.  When  defervescence  commenced  we 
substituted  for  the  potion  water  containing  bicarbonate  of  soda,  4  parts  to  1,000 
as  an  ordinary  drink  (1  to  2  litres). 

Nausea  and  vomiting  was  combatted  with  ice. 

We  present  below  the  clinical  notes  so  that  an  exact  judgment  may  be  formed  as  to 
the  value  of  this  method  of  treatment.  It  must  be  remembered  that  the  statistics  of 
hospitals  give  an  excessive  mortality  not  only  on  account  of  the  gravity  of  the  cases 
received,  but  also  because  of  the  advanced  period  of  sickness  at  the  time  of  admission. 

We  group  our  cases  in  three  classes:  light  cases,  those  which  entered  upon  conva- 
lescence at  the  termination  of  the  first  period;  common  cases,  those  which  passed  to 
the  second  period;  and  grave  cases,  those  which  present  some  symptom  of  gravity. 

Clinical  notes  of  44  cases  are  given  by  the  author  of  the  paper;  of 
these,  11  are  placed  in  the  first  category,  light  cases;  14  in  the  second, 
common  cases,  and  19  in  the  third,  grave  cases. 

The  results  are  summed  up  as  follows: 

Treated 44 

Recovered   ."7 

Died 7 

Mortality , 15.9  percent. 

The  official  statistics  of  jellow  fever  in  the  Mercedes  Hospital  in  previous  years  is 
as  follows: 


Tear. 

Treated. 

EecoTeietl, 

Died. 

^rortality. 

1882 

187 
178 
132 
40 
28 
75 
72 

124 
103 
77 
IC 
11 
33 
38 

63 
75 
55 
24 
17 
42 
34 

I'er  cent. 
33.  C 

42.1 

41. C 

1883 

1SS4 

1885 

1886 

60.7 
56.0 

1887 

1888 

712  j      402 

310 

43.5 

96      ,        ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

Thanks  to  the  courtesy  of  our  confreres  in  the  hospital  we  have  been  able  to  sub- 
mit to  treatment  all  the  cases  admitted,  but  we  have  excluded  two — one  "which 
entered  on  the  seventh  day  with  suppression  of  urine  and  black  vomit,  who  resisted 
all  treatment ;  the  other  entered  ti  hours  before  death  and  was  not  seen  by  us. 
From  the  comparison  made,  it  appears  that  the  Sternberg  treatment  has  diminished 
the  mortality  to  less  than  one-half  the  mean  mortality  of  this  hospital. 

We  have  observed  the  following  facts:  The  patients  have  offered  a  notable  gastric 
tolerance  during  the  medication;  when  treated  from  the  first  day  vomiting  has  rarely 
occurred. 

The  secretion  of  urine  has  always  been  considerable  ;  even  in  the  grave  cases,  when 
death  occurred,  they  did  not  die  anuric  (La  Guard ia).  Anuria  only  occurred  in  an 
evident  manner  in  a  single  case  (case  28). 

From  the  eighth  to  the  tenth  day  it  is  necessary  to  suspend  the  bicarbonate,  to  give 
stimulants  and  to  combat  hemorrhages,  adynamia,  etc.,  by  the  usual  means. 


REPORT. 


The  investigations  to  which  this  report  relates  were  made  in  the  city 
of  Havana  in  the  summers  of  1888  and  1889;  in  the  city  of  Decatur, 
Ala.,  in  the  autumn  of  1888,  nnd  in  the  laboiatories  of  the  Johns  Hop- 
kins University,  where  I  have  continued  my  researches  during  the  in- 
tervals between  my  visits  to  the  infected  localities,  and  since  my  return 
from  Havana,  in  September,  1889,  up  to  the  present  date. 

I.-MATERIAL. 

My  bacteriological  studies  have  been  made  with  material  obtained 
from  forty-three  yellow  fever  cadavers ;  from  "  black  vomit  "  and  feces 
of  patients  in  various  stages  of  the  disease;  and,  for  comparison,  from 
eighteen  cadavers  in  which  death  occurred  from  some  other  disease 
than  yellow  fever,  and  from  feces  of  healthy  individuals. 

The  autopsies  which  have  furnished  me  this  material  are  as  follows: 

No.  1.  Havana,  May  12,1833. — Soldier  in  Military  Hospital;  sick  8  days;  black 
vomit;  albuminous  urine  ;  autopsy  3^  hours  after  death.  Collected  peri- 
cardial fluid,  blood  from  heart,  bile  from  gall  bladder,  urine  from  bladder, 
and  material  from  liver,  kidney,  stomach,  and  intestine. 

No.  2.  Havana,  May  17 ,1Q^S. — Attendant  in  Military  Hospital;  aged  30;  4  months  in 
Cuba  ;  sick  3  days  ;  autopsy  2  hours  after  death.  Collected  material  from 
liver,  spleen,  kidney,  intestine,  and  stomach,  blood  from  heart,  urine  from 
bladder,  and  fluid  from  pericardium. 

No.  3.  HarftHft,  M«(/ 19, 1888.— Soldier  in  Military  Hospital;  sick  6  days;  antopsy  7 
hours  after  death.  Collected  material  from  liver,  kidney,  stomach,  and  in- 
testine, blood  from  heart,  urine  from  bladder,  and  pericardial  fluid. 

No.  4.  Havana,  May  22,1888. — Soldier  in  Military  Hospital;  sick  .5  days.  Collected 
material  from  kidney,  sifleen,  stomach,  and  intestine,  blood  from  heart,  and 
urine  from  bladder. 

No.  G.  Havana,  May  23, 1883. — Soldier  in  Military  Hospital ;  sick  6  days;  autopsy  4 
hours  after  death.  Collected  material  from  liver,  kidney,  stomach,  and  in- 
testine, blood  from  heart,  and  urine  from  bladder. 

No.  0.  Havana,  May  23,  1888. — Soldier  in  Military  Hospital;  autopsy  4  hours  after 
death.  Collected  material  from  liver,  kidney,  stomach,  and  intestine,  blood 
from  heart,  and  urine  from  bladder. 

No.  7.  Havana,  May  2^,1888. — Soldier  in  Military  Hospital ;  sick  4  days;  autopsy  2^ 
hours  after  death.  Collected  material  from  liver,  kidnej^,  stomach,  and  in- 
testine, blood  from  heart,  and  urine  from  bladder. 

No.     8.  Havana,  May  2{\1888. — Soldier  in  Military  Hospital;  sick  0  days;  autopsy  2 
hours  after  death.     Collected  material  from  liver,  kidney,  stomach,  and  in- 
testine, blood  from  heart,  and  urine  from  bladder. 
40G7 7  97 


08  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

No.  9.  Havana,  June  3,  1838. — Soldier  in  Military  Hospital;  sick  5  days;  autopsy  5 
Lours  after  death.  Collected  material  from  liver,  kidney,  stomach,  aud  iu- 
testiue,  blood  from  heart,  and  urine  from  bladder. 

No.  10.  Havana,  June  6,  188>^.— Soldier  iu  Military  Hospital ;  sick  5  days;  autopsy  1 
hour  aud  40  minutes  after  death.  Collected  material  from  liver,  kiduey, 
stomach,  and  intestine,  blood  from  heart,  aud  urine  from  bladder. 

No.  11.  Decatur,  Ala.,  Octoler  3,  1883.— Male,  aged  35  years;  sick  3  days;  autopsy  1 
hour  after  death.  Collected  material  from  liver,  kiduey,  stomach,  andin- 
testiue. 

No.  \2.  Decatur,  Ala.,  October  b,  1888.— Male,  aged  35  years;  autopsy  U  hours  after 
death.     Collected  material  from  liver,  kidney,  stomach,  and  intestine. 

No.  13.  Decatur,  Ala.,  Octuher  8,  1888.— Male,  aged  40;  sick  5  days;  autopsy  2  hours 
after  death.  Collected  material  from  kiduey,  liver,  stomach,  and  intes- 
tine. 

No.  14.  Havana,  April  23,  1889.— Soldier  in  Military  Hospital;  sick  5  days;  autopsy 
9  hours  after  death.  Collected  material  from  spleen,  liver,  kiduey,  stom- 
ach, and  intestine,  blood  from  heart,  aud  uriue  from  bladder. 

No.  15.  Havana,  AprU  28,  1889.- Soldier  iu  Military  Hospital;  sick  10  days;  autopsy 

9  hours  after  death.     Collected  material  from  liver,  kidney,  stomach,  and 
intestine,  blood  from  heart,  aud  uriue  from  bladder. 

No.  15.  Havana,  May  5,  1889. — Soldier  in  Military  Hospital;  sick  7  days;  autopsy 

13^  hours  after  death.    Collected  material  from  liver,  kidney,  stomach,  and 

intestine. 
No.  17.  Havana,  May  12,  1889.— Soldier  iu  Military  Hospital ;  sick  5  days ;  autopsy 

5  hours  after  death.     Collected  material  from  liver,  kiduey,  stomach,  and 

iutestine,  blood  from  heart,  aud  urine  from  bladder. 
No.  18.  Havana,  May  13,  18c9.— Patient  in  Civil  Hospital;  male,  aged  28  years;  sick 

5  days;  autopsy  2  hours  after  death.    Collected  material  from  liver,  kiduey, 
stomach,  aud  intesliue,  and  blood  from  heart. 

No.  19.  Havana,  May  22,  1889.— Soldier  in  Military  Hospital ;  sick  5  days ;  autopsy 

6  hours  after  death.    Collected  material  from  liver,  stomach,  and  intestine, 
and  blood  from  heart. 

No.  20.  Havana,  May  26,  1889. — Patient  in  Civil  Hospital ;  autopsy  9  hours  after 

death.     Collected  material  from  liver,  stomach,  aud  intestine. 
No.  21.   Havana,  May  27,  1889.— Soldier  in  Military  Hospital ;  sick  7  days;  autopsy 

10  hours  after  death.     Collected  material  from  liver  and  iutestine. 

No.  22.  Havana,  June  4,  1889. — Soldier  iu  Military  Hospital ;  sick  5  days.  Collected 
material  from  liver,  stomach,  and  Intestine. 

No.  23.  Havana,  June  4,  1889. — Soldier  in  Military  Hospital;  sick  8  days;  autopsy 
10  hours  after  death.  Collected  material  from  liver,  stomach,  aud  intes- 
tine. 

No.  24.  Havana,  Jane  13,  1639. — Soldier  in  Military  Hospital  ;  sick  5  days;  autopsy 
4^  hours  after  death.  Collected  material  from  liver,  kidney,  stomach,  and 
iutestine. 

No.  25.  Havana,  June  29,  1889. — Soldier  in  Military  Hospital;  sick  9  days;  autopsy 
lOj  hours  after  death.  Collected  material  from  liver,  stomach,  and  intestine. 

No.  26.  Havana,  July  1,  1889. — Soldier  in  Military  Hospital;  sick  9  days,  autopsy  5 
hours  after  death.  Doubtful  case;  the  diagnosis  is  not  suj)ported  by  the  patho- 
logical appearances.    Excluded. 

No.  27.  Havana  July  3,  1889. — Patient  in  Civil  Hospital;  sick  7  days  ;  autopsy  1  hour 
aud  15  minutes  after  death.  Collected  material  from  liver,  stomach,  and 
intestine. 

No.  28.  Havana,  July  15,  1889. — Soldier  iu  Military  Hospital  ;  autopsy  6  hours  after 
death.     Collected  material  from  liver,  stomach,  aud  iutestine. 

No.  29.  Havana,  July  29,  1889.— Soldier  iu  Military  Hospital;  sick  6  days;  autopsj' 
5  hours  after  death.   Collected  material  from  liver,  stomach,  aud  iutestine. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER,  99 

No.  30.  ZT^at^aHa,  4m.(7ms<U,  1889.— Soldier  in  Military  Hospital;  sick  7  days ;  autopsy 
7i  hours  after  death.  Collected  material  from  liver,  stomach,  and  intestine. 

No.  31.  Havana,  August  10,  1889. — Patient  in  Civil  Hospital,  male,  aged  41 ;  sick  6 
days;  autopsy  6  hours  after  death.  Collected  material  from  liver,  stom- 
ach, and  intestine. 

No.  32.  Havana,  August  12,  1889. — Soldier  in  Military  Hospital;  sick  5  days;  autopsy 

6  hours  after  death.     Collected  material  from  liver,  stomach,  and  intestine. 
No.  .33.  Havana,  August  \^,\?i9Q. — Soldier  in  Military  Hospital ;  sick  7  days;  autopsy 

7  hours  after  death.     Collected  material  from  liver,  stomach,  and  intestine. 
No.  34.  Havana,  August  \?,,\SS'd. — Soldier  in  Military  Hospital ;  sick  9  days;  autopsy 

3  hours  after  death.     Collected  material  from  liver. 
No.  35.  Havana,  August  1.5,  1889. — Soldier  in  Military  Hospital ;  sick  5  days;  autopsy 

5  hours  after  death.     Collected  material  from  liver  and  intestine. 
No.  36.  Havana,  August  19, 1889. — Soldier  in  Military  Hospital;  sick  6  days;  autopsy 

5  hours  after  death.     Collected  material  from  liver  and  intestine. 

No.  37.  Havana,  August  2\,\S'ii'd. — Soldier  in  Military  Hospital;  sick  4  days;  autoj)sy 

6  hours  after  death.     Collected  material  from  liver  and  intestine. 

No.  38.  Havana,  August  22,  1889. — Soldier  in  Military  Hospital;  sick  .5  days;  autopsy 
6^  hours  after  death.     Collected  material  from  liver  and  intestine. 

No.  39.  Havana,  August  24,  1889. — Patient  in  Civil  Hospital ;  male,  aged  23  ;  sick  10 
days;  autopsy  2  hours  after  death.     Collected  material  from  liver. 

No.  40.  Havana,  August  2^,  ISa^. — Soldier  in  Military  Hospital ;  sick  4  days;  autopsy 
6  hours  after  death.     Collected  material  from  liver. 

No.  41.  Havana,  August  26,  1889. — Patient  in  Civil  Hospital;  sick  7  days;    autopsy 

8  hours  after  death.     Collected  material  from  liver. 

No.  42.  Havana,  August  26,  188'^. — Patient  in  Civil  Hospital ;  autopsy  4  hours  after 

death.     Collected  material  from  liver. 
No.  43.  Havana,  August  26,  1889. — Soldier  in  Military  Hospital;  sick  7  days;  autopsy 

6  hours  after  death.     Collected  material  from  liver. 

COMPARATIVE   AUTOPSIES. 

No.    1.  Havana,  Mag  17,  1889. — Case  of  tuberculosis  in  Civil  Hosi)ital ;  autopsy  2  hours 

after  death.     Collected  material  from  liver  and  kidney. 
No.    2.  Havana,  May  19,  1889. — Case  of  tuberculosis  in  Civil  Hospital ;  autopsy  If 

hours  after  death.     Collected  material  from  liver  and  kidney. 
No.    3.  Havana,  May  22,  1889. — Case  of  heart  disease  in  Civil  Hospital.     Collected 

material  from  liver. 
No.    4.  Havana,  May  25,  1889. — Case  of  abscess  of  liver  in  Civil  Hospital;  autopsy  1^ 

hours  after  death.     Collected  material  from  liver. 
No.  5.  Havana,  Mag  25,   1889. — Insane    woman  in    civil   hospital.     Brain  disease; 

autopsy  5  hours  after  death.     Collected  material  from  liver. 
No.  6.  Havana,  May  30,   1889. — Case  of  tuberculosis  in    civil  hospital;    autopsy  6 

hours  after  death.     Collected  material  from  liver. 
No.  7.  Havana,  June  2,  1889. — Case  of   heart  disease  in  civil  hospital;    autopsy  5 

hours  after  death.     Collected  material  from  liver. 
No.  8.  Baltimore,  October  30,  18o9. — Case  of  tuberculosis  in  Johns  Hopkins  Hospital; 

autopsy  8  hours  after  death.     Collected  material  from  liver. 
No.  9.  Baltimore,  November  12, 1889. — Case  of  tuberculosis  in  .Johns  Hopkins  Hospital; 

autopsy  CA  hours  after  death.     Collected  material  from  liver. 
No.  10.  Baltimore,  November  18,  1889. — Case  of  osteomyelitis  of  tibia  with  amyloid 

liver  and  kidney.     Collected  material  from  liver. 
No.  11.  Baltimore,  November  23, 1889. — Case  of  tuberculosis  in  Johns  Hopkins  Hospital; 

autopsy  24  hours  after  death.     Collected  material  from  liver. 
No.  12.  Baltimore,  November  25, 1889. — Case  of  tnberculosis  in  Johns  Hopkins  Hospital; 

autopsy  8  hours  after  death.     Collected  material  from  liver. 


100  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

No.  13.  Baltimore,  Xovemher30,  1889. — Death  from  cblorolbrm;  autopsy  at  once  by  Dr. 

Keirle,  of  Baltimore.     Collected  material  from  liver. 
No.  14.  Baltimore,  November  dO,  1889. — Case  of  heart  disease  in  Johns  Hopkins  Hospital, 

Baltimore;  autopsy  7  hours  after  death.     Collected  material  from  liver. 
No.  15.  Baltimore,  January  2,   1890. — Peritonitis   following  laparotomy"  for  ovarian 

tumor.     Case  in  Johns  Hopkins  Hospital.     Collected  material  from  liver. 
No.  16.  Baltimore,  January  6,  1890. — Death  in  10  minutes  after  tapping  of  abdominal 

cavity.     Case  of  fibro-cystic  tumor  of  uterus  in  Johns  Hojikins  Hospital; 

autopsy  4  hours  after  death.     Collected  material  from  liver. 
No.  17.  Baltimore,  January  13,  1890. — Case  of  heart  disease,  Johns  Hopkins  Hospital; 

autopsy  4  hours  after  death.     Collected  material  from  liver. 
No.  18.   Baltimore,  January  14,  1890. — Pneumonia.      Case  in' Johns  Hopkins  Hospital; 

autopsy  "24  hours  after  death.     Collected  material  from  liver. 

MATERIAL   COLLECTED   FROM   YELLOW-FEVER    CASES   DURING   LIFE. 

Havana,  May  6,  1888. — Collected  black  vomit   and  melanotic  discharge  from  bowels. 

Case  in  military  hospital,  fifth  day  of  disease. 
Havana,  May  5,  1838. — Cultures  made  from  surface  of  body  of  cases  in  civil  hospital 

No.  1.  Yellow  fever  convalescent. 

No.  2.  Case  of  rheumatism. 

No.  3.  Case  of  typhoid  fever. 

No.  4.  Attendant  in  hospital. 

No.  5.  Case  of  yellow  fever  with  black  vomit,  fifth  day  of  sickness. 

No.  6.  Dr.  Finlay. 
Havana,  May  29, 1888. — Collected  vomit  from  yellow  fever  cases  in  military  hospital : 

No.  1.  Sick  3  days;  vomit  transparent;  acid. 

No.  2.  Sick  2  days ;  vomit  transparent ;  acid. 

No.  3.  Sick  2  days  ;  vomit  transparent ;  acid. 
Havana,  June  4,  1888.— Collected  vomit   from  patient  in  Garcini  Hospital';  sick  3 

days;  vomit  transparent ;  alkaline. 
June  5. — Collected  "  coffee  ground"  vomit  from  same  case  ;  acid. 
Havana,  June  A,  1888. — Collected  vomit  from  case  in  Garcini  Hospital;  transparent; 

acid. 
Havana,  July  5,  1889. — Collected  typical  black  vomit  from  case  in  civil  hospital; 
sick  7  days. 

SPECIMENS  OF  FECES  COLLECTED  AND  EXAMrNED  IN  DECATUB,  ALA.  (1888),  AND 

IN  HAVANA  (1889). 

Case  1.   Octoier  3. — Sick  48  hours;  thin,  yellow  color ;  neutral  reaction. 

Case  2.   OctoherQ. — Sick  60  hours  (fatal  case);  thin,  yellow  color;  neutral  reaction. 

Case  3.  October  6. — Sick  72  hours  (fatal  case)  ;  mucus,  without  color;  neutral  reac- 
tion. 

Case  4.  October  7. — Sick  12  hours  (fatal  case) ;  reaction  neutral. 

Case  5.   October  8. — Sick  36  hours;  thin,  pale  yellow;  neutral  reaction. 

Case  6.   October  9. — Sick  48  hours;  thin,  pale  yellow  ;  neutral  reaction. 

Case  7.   October  9. — Sick  4  hours  ;  thin,  pale  yellow  ;  slightly  acid. 

Case  8.  October  10. — Sick  24  hours  (fatal  case);  thin,  light  yellow  color;  slightly 
acid  reaction. 

Case  9.   Oc/o&e?- 10.— Sick  24  hours;  thin,  light-yellow  color  ;  neutral. 

Case  10.   October  14. — Sick  3  days  (fatal  case)  ;  thin,  pale  yellow  color ;  neutral. 

Case  11.   October  15. — Sick  12  hours. 

Case  12.   October  15. — Sick  2  days  (fatal  case);  thin,  pea-soup  color;  neutral. 

Case  13.  October  IG. — Sick  3  days;  thin,  brown  color;  slightly  acid. 

Case  14.  October  16. — Sick  2  days. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  101 

Case  15.  Octolcr  17.— Sick  313  hours  (fatal  case)  ;  very  tUiu,  bright  yellow  color;  neU' 

tral. 
Case  16.  October  18.— Sick  50  hours  (fatal  case) ;  thin,  clay-colored  ;  slightly  acid. 
Case  17.   October  19.— Sick  3  days  (fatal  case) ;  thin,  dark-brown  color. 
Case  18.   Odo&fj- 23.— Sick  48  hours  ;  very  thin,  pale  yellow  ;  neutral  reaction. 
Case  19.  October  23.— Sick  2  days  ;  thin,  pale  yellow  color  ;  neutral. 
Case  20.  October  25. — Sick  48  hours  ;  thin,  brown  color;  alkaline  reaction. 
Case  21.   Octo&er  27.— Sick  36  hours  (fatal  case);  thin,  color  of  pea  soup  ;  neutral. 

Same  case  ;  third  day  ;  thin,  light  yellow  ;  neutral. 
Case  22.  Octobtr  23.— Sick  24  hours  ;  thin,  color  of  pea  soup  ;  neutral. 
Case  23.  October  30.— Sick  24  hours ;  very  thin,  pale  yellow  ;  neutral. 
Case  24.— Sick  3  days. 
Case  25. — Sick  24  hours. 
Case  26. — Sick  5  days. 
Case  27. — Sick  48  hours. 
Case  28.— Sick  30  hours. 
Case  29.— Sick  48  hours. 
Case  30. — Sick  36  hours. 
Case  31. — Sick  36  hours. 
Case  32. — Sick  36  hours. 
Case  33.— Sick  48  hours. 
Case  34.— Sick  24  hours. 
Case  35. — Sick  24  hours. 

The  material  from  cases  25  to  3G,  inclusive,  was  collected  in  Decatur 
by  my  assistant,  Dr.  Littlejolin,  and  sent  to  me  at  Baltimore,  wliere  the 
bacteriological  examination  was  made. 

At  mj' request.  Dr.  Littlejohn  also  sent  me  feces  from  fifteen  healthy 
persons  and  convalescents,  for  comparison. 

Case  37.  Havana,  July  1,  1889. — Collected  feces  from  case  in  civil  hospital;  sick  7 
days  ;  very  low,  a  milky  looking  fluid,  with  acid  reaction. 

Case  38.  Havana,  July  2,  1839. — Collected  feces  from  case  on  board  German  brig  ;  sick 
5  days;  thin,  light  yellow,  alkaline. 

Case  39.  Havana,  July  4,  1889. — Collected  feces  from  case  in  civil  hospital;  sick  5 
days;  thin,  yellow  color,  alkaline. 

Note. — The  alkaline  reaction  of  the  feces  in  many  of  these  cases 
was  no  doubt  due  to  the  fact  that  they  were  on  an  allialine  treatment. 


II-METHOD    OF  COLLECTING  MATERIAL 


I  am  in  the  habit  of  using  as  collecting  tubes  the  glass  bulbs  with  a 
long  neck,  described  by  me  In  a  paper  read  before  the  American  Asso- 
ciation for  the  Advancement  of  Science  in  August  1881.  The  form 
is  shown  in  Fig.  1. 

These  are  thoroughly  sterilized  and  hermetically  sealed 
when  made.  I  always  carry  a  large  supply  of  them  "  into 
the  field"  with  me,  as  they  serve  for  various  purposes,  as 
will  hereafter  be  shown. 

The  modus  operandi  of  collecting  material  at  an  autopsy, 
as  usually  practiced  b}^  me,  is  as  follows :  I  expose  the 
abdominal  viscera  by  making  an  incision  from  the  superior 
spinous  process  of  the  illium  on  one  side,  in  a  line  parallel 
with  the  long  axis  of  the  body  up  to  the  margin  of  the  ribs, 
then  across  to  a  corresponding  point  on  the  opposite  side 
and  down  to  the  other  superior  spinous  process.  The  large, 
apron-like  tlap  consisting  of  the  entire  anterior  wall  of  the 
abdominal  cavity  is  thrown  back,  and  gives  free  access  to 
the  viscera  contained  in  this  cavity. 

It  is  best  to  collect  from  the  solid  viscera  first.  The  liver 
is  drawn  down  a  little  with  a  tenaculum  or  forceps  and  a 
hot  spatula  is  applied  to  a  point  upon  its  surface.  This 
insures  the  destruction  of  any  microorganisms  which  may  have  fallen 
upon  the  surface,  or  which  might  be  in  the  cavity  of  the  abdomen  be- 
fore opening  it.  The  spatula  is  held  in  position  by  an  assistant  until  I 
am  ready  to  introduce  the  collecting  tube.  The  long  stem  of  this  is 
passed  through  the  flame  of  an  alcohol  lamp  to  sterilize  the  exterior, 
the  bulb  is  heated  to  expand  the  contained  air,  and  the  sealed  extremity 
of  the  tube  is  then  broken  off  with  sterilized  forceps.  Tbe  preliminary 
heating  of  the  bulb  is  to  prevent  a  sudden  inrush  of  air,  by  which 
atmospheric  organisms  might  occasionally  gain  access  to  the  bulb.  The 
extremity  of  the  stem  is  then  passed  into  the  organ  at  the  point  where 
the  hot  spatula  had  been  applied. 

The  air  in  the  bulb  being  somewhat  rarefied  by  the  heat  applied, 
there  is  a  suction  force  as  it  cools,  and  blood  from  the  organ  is  drawn 
into  the  tube. 

In  order  to  obtain  at  the  same  time  crushed  tissue,  I  move  the  tube 
backwards  and  forwards  so  as  to  lacerate  and  crush  the  parenchyma 

102 


Fig.  1. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  103 

of  the  organ  witli  its  broken  extremity.  By  this  means  I  am  able  to 
obtain  from  the  liver,  the  spleen,  or  the  kidney  a  considerable  qnan- 
tity  of  crushed  parechyma  mixed  with  blood  without  any  possible  con- 
tamination by  microorganisms  from  without.  As  soon  as  the  collection 
is  made  the  extremity  of  the  tube  is  sealed  in  an  alcohol  lamp.  Mate- 
rial from  the  hollow  viscera  is  obtained  in  the  same  way.  The  hot  spat- 
nla  is  applied  to  a  convenient  point  on  the  walls,  and  the  broken  end 
of  the  sterilized  tube  is  forced  through  at  this  point.  My  collections  of 
urine  through  the  walls  of  the  bladder,  of  material  from  the  stomach 
and  intestine,  and  of  blood  from  the  heart  have  all  been  made  in  this 
w^ay.  I  am  in  the  habit  of  making  a  separate  opening  through  the  chest 
walls  over  the  heart,  as  I  consider  it  a  safer  method  than  to  reach  the 
heart  by  cutting  through  the  diaphragm. 

Pieces  of  tissue  for  future  histological  study  are  cut  into  small  frag- 
ments and  at  once  placed  in  strong  alcohol  or  in  Mueller's  fluid. 


III-METHODS  OF  RESEARCH. 

The  following-  are  the  principal  methods  of  research  employecl. 

{a)     THE   DIRECT   EXAMINATION   OF    "SMEAR    PREPARATIONS"    FROM 
THE   BLOOD  AND   TISSUES  FOR  MICROORGANISMS. 

I  have  made  this  examination  in  the  entire  series  of  cases  in  which 
I  have  made  autopsies.  Usually  I  have  stained  these  preparations 
with  an  aqueous  solution  of  fuchsin,  or  with  Loeffler's  solution  of 
methyline  blue.  I  prefer  the  fuchsin  solution  because  it  stains  very 
promptly  all  of  the  bacteria  with  which  I  am  acquainted ;  and  I  feel 
very  confident  that  with  my  one-eighteenth  inch  hom.  oil  im,  objective 
of  Zeiss,  the  Abbe  condenser,  and  a  fuchsiustained  "smear  prepara- 
tion" from  the  blood,  liver,  or  kidney,  any  microorganism  of  this  class 
which  might  be  present  should  be  easily  seen. 

[h]  AiiROBiC  CULTURES  IN  FLESH-PEPTONE-GELATINE,  IN  AGAR-AGAR 

JELLY,  ETC. 

lu  the  whole  series  of  cases  I  have  introduced  some  of  the  material 
collected  as  heretofore  described  into  one  or  the  other  of  these  media, 
and  often  in  both.  Immediately  upon  my  return  to  the  laboratory  after 
making  an  autopsy  I  am  in  the  habit  of  putting  up  Esmarch  roll-tubes 
from  the  material  collected,  and  these  are  kept  under  observation,  at  a 
proper  temperature,  for  several  da^'s  at  least.  In  tube  Ko.  1  of  a  scries 
of  three  Esmarch  roll-tubes  I  commonly  introduce  two  or  three  drops 
of  blood,  or  of  crushed  liver  tissue,  etc.,  so  that  any  microorganism 
capable  of  growing  in  the  culture  medium  employed  would  be  revealed, 
by  the  development  of  colonies,  even  if  present  in  very  small  numbers. 

In  Cuba,  during  the  months  of  March  and  April  I  kept  an  incubating 
oven  running  at  a  temperature  of  35°  to  37°  C,  but  later,  during  the 
epidemic  season,  I  took  it  for  granted  that  artificial  heat  would  not  be 
necessary  to  insure  the  development  of  the  particular  germ  I  was  in 
search  of.  Of  course  our  usual  medium  for  plate  cultures — flesh-pep- 
tone-gelatine containing  10  per  cent,  of  gelatine — was  not  available  in 
Havana  during  the  summer  months  without  resorting  to  the  use  of  a 
refrigerator.  I  found,  however,  that  when  the  medium  contained  20 
per  cent,  of  gelatine  it  would  stand  a  temperature  of  28°  C.  (82.4°  F.), 
and  I  was  able  to  use  it  without  a  refrigerator  during  tlie  months  of  May 
and  June.  Later  a  refrigerator  was  required  even  for  the  20  per  cent, 
gelatine  medium.  This  contained  a  chamber  which  I  was  able  to  main- 
tain at  a  temperature  of  about  27°  C. 

104 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVEE. 


105 


So  far  as  I  could  see^tbis  20  per  cent,  gelatine  answered  quite  as  well, 
as  a  culture  medium,  as  that  made  in  accordance  with  Koch's  standard 
formula,  wliicli  contains  10  per  cent,  of  gelatine.  Liquefying  organisms 
caused  liquefaction  as  usual,  and  non-liquefying  organisms  formed 
colonies  in  Esraaich  roll-tubes,  and  grew  freely  in  "  stick  cultures.'' 
But  the  advantages  of  an  agar  medium  were  apparent,  and  I  accord- 
ingly used  this  very  extensively  for  my  roll-tubes,  and  especially  with 
the  addition  of  5  per  cent,  of  glycerine.  Many  of  the  mici'oorganisms 
which  I  encountered  and  shall  hereafter  describe,  grew  luxuriantly  in 
this  medium.  I  also  made  cultures  in  an  agar  or  gelatine  medium  con- 
taining 0.2  i)er  cent,  of  hydrochloric  acid.  Quite  a  number  of  the  bacilli 
which  I  have  isolated  grew  freely  in  this  acid  medium. 

I  have  also  tested  the  growth  of  the  various  organisms  studied  by 
me  upon  potato;  and  for  this  purpose  have  used  the  cylindrical  pieces 
of  potato,  cut  with  a  slanting  surface  and  sterilized  in  an  ordinary  test 
tube  as  first  recommended  by  Meade  Bolton. 

Cultures  have  also  been  made  in  various  other  media,  such  as  blood 
serum,  veal  broth,  and  agua  coco.  The  last-mentioned  liquid  I  have 
used  extensively  and  find  that  for  a  large  class  of  microorganisms  it 
constitutes  a  very  favorable  nutrient  medium. 

(c)    ANAiiROBIC    CULTURES. 

I  made  no  anaerobic  cultures  in  1888,  but  the  following  year  did  so 
in  a  considerable  number  of  cases.  In  these  I  used  for  the  most  part 
agar  jelly  with  5  per  cent,  of  glycerine. 

The  blood  or  liver  tissue  from  one  of  my  collecting  tubes  was  intro- 
duced into  the  liquefied  medium  ke^jt  at  a  proper 
temperature  in  a  warm  bath  {iO°  C),  and  a  cur- 
rent of  purified  hydrogen  allowed  to  pass  through 
it  long  enough  to  insure  the  exclusion  of  oxygen — 
usually  half  an  hour  or  more.  My  method  is  as 
follows : 

Soft  rubber  corks  having  two  perforations  for 
the  i)assage  of  glass  tubes  are  cut  into  sections; 
these  are  placed  for  sometime  in  1:1000  solution 
of  mercuric  chloride  to  sterilize  them,  and  then,  in 
a  wide-mouthed  bottle,  having  a  ground-glass  stop- 
per, in  strong  alcohol.  When  one  of  these  is  to  be 
used  it  is  taken  from  the  alcohol  with  sterilized 
forceps  and  the  alcohol  is  removed  by  burning. 
A  long  and  a  short  glass  tube  are  passed  through 
this  rubber  stopper,  and  removing  the  cotton  plug 
from  a  test  tube  in  which  the  anaerobic  culture  is 
to  be  made  it  is  placed  as  in  Fig.  2  (a).  The  long 
tube,  previously  sterilized  by  heat,  must  pass  nearly  to  the  bottom  of  the 
liquefied  agar.     A  space  of  half  an  inch  or  more  is  left  above  the  rubber 


Fig,  2. 


106 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


stopper,  and  this  I  fill  with  melted  sealing-  wax.  I  have  found  by  ex- 
perience that  the  rubber  stopper  alone  can  not  be  relied  upon  to  retain 
the  hydrogen,  no  matter  how  accurately  it  fits  the  test  tube.  Nor  have 
1  had  good  success  in  the  use  of  melted  paraffine.  This  has  a  tendency 
to  retract  from  the  glass  walls  of  the  test  tube,  and  in  practice  I  find 
that  as  a  rule  the  hydrogen  soon  escapes  from  a  tube  closed  in  this  way. 
It  will  be  seen  that  my  rubber  stopper  serves  cliiefly  to  support  the 
glass  tubes,  and  the  melted  sealing  wax,  upon  which  I  depend  for  the 
complete  sealing  up  of  the  mouth  of  the  test  tube.  The  sections  of 
rubber  stoppers  are  of  various  diameters,  and  it  is  easy  to  select  one 
which  will  fit  the  test  tube  employed. 

The  long  glass  tube  is  now  connected  with  the  hydrogen  apparatus 
and  the  test  tube  is  left  in  the  warm  bath  to  keep  the  agar  jelly  from 
becoming  solid.  At  the  end  of  half  an  hour  the  outlet  tube  h  is  sealed 
in  the  flame  of  an  alcohol  lami),  and  in  the  same  way  the  inlet  tube  c 
The  liquefied  agar  is  then  spread  upon  the  walls  of  the  test  tube  in  the 
usual  manner,  by  turning  it  upon  a  block  of  ice. 

I  have  at  times  varied  this  procedure  as  follows:  The  liquefied  agar 
jelly,  or  flesh  peptone-gelatine,  to  which  blood  or  liver  tissue,  etc.,  has 
been  added,  is  first  made  into  an  Esinarch  roll-tube;  the  cotton  plug 

(a),  or  a  portion  of  it,  is  then  i)ushed 
up  into  the  tube  apd  a  rubber  stopper 
[h)  carrying  two  short  glass  tubes  is 
put  in  position.  The  end  of  the  test 
tube  is  then  filled  with  sealing  wax  as 
before.  Hydrogen  is  now  passed  into 
the  test  tube  by  coupling  one  of  the 
short  glass  tubes  with  a  hydrogen  ap- 
paratus. The  test  tube  is  sustained  in 
an  inverted  position,  (see  Fig.  3),  so  that 
the  action  of  gravity  may  come  into 
play  in  displacing  the  oxygen.  This 
plan  is  more  convenient  than  the  pre- 
ceding one,  and  the  only  objection  to 
it  is  the  fact  that  a  certain  amount  of 
oxygen  may  be  retained  in  the  solidi- 
fied agar  jelly  covering  the  walls  of 
the  tube.  But  if  the  hydrogen  is 
passed  for  a  considerable  time  it  would  certainly  seem  that  the  greater 
part  of  the  oxygen  must  escape  by  diftusion  from  this  thin  layer. 
Certainly  any  but  the  most  strictly  anaerobic  organisms  should  grow 
in  a  tube  prepared  in  this  way,  if  the  medium  is  suitable  for  it. 

I  have  varied  the  medium  at  times  by  mixing  the  agar  jelly  with  flesli- 
l)eptone-gelatin,  or  with  blood  serum.  This  is  easily  done  when  the 
method  last  described  is  employed,  but  not  when  the  hydrogen  is  allowed 
to  bubble  through  the  liquified  medium;  for  in  this  case  the  addition 


Fig.  3. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVEE. 


107 


Fig.  4. 


of  gelatin  or  of  blood  serum  causes  the  tube  to  be  filled  with  bubbles, 
so  that  it  can  not  be  made  into  an  Esmarch  roll-tube. 

To  add  blood  serum  to  our  agar  or  gelatin  medium,  without  con- 
tamination which  would  call  for  subsequent  sterilization,  I  use  the 
bulbs  with  a  long  neck  already  described  as  collecting  tubes. 

Blood  from  a  sheep,  or  some  other  suitable  animal,  is  first  drawn 
from  a  large  artery — femoral  or  carotid — into  a  sterilized  Wolff's  bottle, 
(Fig.  4).  The  inlet  tube  h  is  introduced 
directly  into  theartery  and  astheblood 
flows  the  air  escapes  through  the  cot- 
ton filter.  When  proper  i)recautions 
are  taken  the  blood  in  the  receiving 
bottle  will  be  sterile,  and  after  the 
serum  has  separated  it  can  be  trans- 
ferred to  the  bulbs  referred  to  without 
any  danger  of  contamination,  and  con- 
sequently without  any  necessity  for 
sterilization  by  heat.  This  is  accom- 
])lished  by  breaking  off  the  sealed  end 
of  the  tube  a,  which  has  previously 
been  notched  with  a  file,  and  introduc- 
ing into  the  clear  blood  serum  tiie 
sterilized  stem  of  a  collecting  tube, 
the  l)ulb  having  been  gently  heated 
in  the  flame  of  a  lamp.  The  serum  mounts  into  the  bulb  and  when  it 
contains  a  suflBcient  quantity-it  is  withdrawn  and  another  introduced 
in  its  place.  Thus  one  after  another  is  charged,  and  immediately  the 
extremity  of  the  stem  is  sealed  in  the  flame  of  a  Bunsen  burner  or  an 
alcohol  lamp.  It  is  a  great  convenience  to  have  a  supply  of  sterile 
blood  serum  always  ready,  and  I  keep  a  stock  on  hand  preserved  in  this 
way.  Not  only  are  culture  liquids  preserved  in  this  way  safe  from  con- 
tamination but  these  tubes  are  convenient  to  transport,  and  the  trans- 
fer of  the  liquid  medium  to  a  test  tube  is  easily  and  safely  effected. 
Breaking  off  the  end  of  the  stem  with  sterilized  forceps,  and  introduc- 
ing it  beside  the  cotton  stopper  of  a  sterilized  test  tube,  the  contents 
of  the  bull)  are  forced  out  by  applying  gentle  heat  to  the  portion  filled 
with  air. 

I  have  a  small  alcohol  lamp  always  at  hand  for  this  purpose.  In  this 
way  I  am  able  to  make  mixtures  of  blood  serum  and  agar  jelly,  or  gel- 
atin, and  to  make  Esmarch  roll-tubes  containing  the  uncoagulated  al- 
bumen of  the  blood  serum.  This  maybe  a  decided  advantage  under 
certain  circumstances,  as  our  ordinary  culture  media  contain  but  little 
albumen  after  being  sterilized  at  a  high  temperature. 

{d}  EXAMINATION   OF   TISSUES  KEPT   FOR  FORTY-EIGHT  HOURS  IN  AN 
ANTISKPTIC   WRAPPING. 

In  those  diseases  which  have  been  proved  to  be  due  to  the  presence 
of  micruorganisms  in  the  blood  or  tissues,  these  microorganisms  may 


108     ETIOLOGY  AND  PREVENTJOX  OF  YELLOW  FEVER. 

be  demonstrated  by  the  methods  heretofore  referred  to  and  by  the  ex- 
amiuation  of  properly  stained  sections  of  the  tissues  involved.  But  in 
one  disease,  at  least — typhoid  fever — cultures  from  the  blood  commonly 
give  a  negative  result,  and  the  bacilli  which  are  present  in  scattered 
groups,  or  colonies,  in  the  spleen,  the  mesenteric  glands,  etc.,  are  not 
always  easily  found. 

Fraenkel  and  Simmonds*  have  shown  that  in  the  spleen  removed  from 
a  person  dying  of  this  disease  the  typhoid  bacillus  multiplies  after 
death,  and  that  numerous  colonies  may  be  found  in  portions  of  the 
organ  which  have  been  left  for  24  to  48  hours  before  being  placed  in 
alcohol,  when  other  pieces  placed  in  alcohol  soon  after  death  show  but 
few  colonies  or  none  at  all. 

I  have  followed  this  hint,  and  in  most  of  my  autopsies  have  kept  a 
piece  of  liver  in  an  antiseptic  wrapping  for  48  hours,  and  have  then 
examined  the  interior  of  the  piece  for  microorganisms  by  the  usual 
methods. 

My  method  has  been  to  take  a  i^iece  of  liver  or  kidney  'the  size  of  a 
man's  fist,  and  to  wash  it  in  a  bath  containing  1  part  of  bichloride  of 
mercury  to  500  parts  of  water.  I  then  envelope  it  in  numerous  folds 
of  thin  tissue  paper  and  again  place  it  in  the  antiseptic  bath,  wetting 
the  tissue  paper  thoroughly  ;  after  which  successive  wrappings  of  dry 
tissue  paper  are  applied,  and  the  piece  is  i)laced  in  a  clean  jar  and  kept 
in  the  laboratory  for  48  hours. 

{e)   EXPERI^IENTS  UPON   ANIMALS. 

I  have  made  numerous  experiments  upon  rabbits,  guinea-pigs,  and 
dogs,  for  the  r)urpose  of  testing  the  i^athogenic  power  of  the  various 
microorganisms  which  I  have  obtained  from  yellow  fever  cadavers. 
The  results  of  these  experiments  will  be  detailed  in  the  proper  place. 
The  method  of  injecting  microorganisms  suspended  in  a  liquid  into  the 
subcutaneous  tissues  or  abdominal  cavity  of  one  of  the  lower  animals 
which  I  have  found  most  satisfactory  and  have  practiced  for  several 
years,  is  as  follows: 

My  bulbs  with  a  long  stem  serve  me  as  a  syringe,  and  I  tind  that 
they  have  decided  advantages  over  any  form  of  hypodermic  syringe. 
The  piston  of  the  ordinary  hypodermic  syringe  is  hard  to  sterilize,  and 
there  is  always  more  or  less  danger  that  with  this  instrument  we  may 
iuject  some  other  microorganism  along  with  the  one  which  we  propose 
to  test.  The  recent  death  of  a  Vienna  bacteriologist  from  the  use  of  a 
syringe  upon  himself  which  he  had  previously  used  to  inject  a  culture 
of  the  glanders  bacillus  into  one  of  the  lower  animals  is  an  unfortunate 
illustration  of  this  fact.  Koch's  syringe,  which  has  a  rubber  ball  by 
which  air  is  forced  into  the  syringe,  taking  the  place  of  a  piston,  is 
much  better.  But  I  prefer  to  employ  my  improvised  syringe,  which*is 
still  safer,  so  far  as  the  accidental  introduction  of  microorganisms  is 

*  Die  ^fciologisclie  Bedeutung  des  Typhus-bacillus,  1886. 


ETIOLOGY    AND    PEEVENTION    OF    YELLOW   FEVER.  109 

concerned.  Tbis  is  used  but  a  single  time,  as  I  find  it  easier  to  make 
new  bulbs  than  to  clean  those  which  ha\^e  been  once  used.  If  the  cul- 
ture has  been  made  in  one  of  these  bulbs,  it  is  all  ready  to  inject ;  if 
not,  it  is  introduced  in  the  usual  way,  bj-  gently  heating  the  bulb  to  form 
a  partial  vacuum.  To  make  the  injection  I  first  cut  away  the  hair  of  the 
animal  with  scissors,  and  then  with  a  pair  of  curved  scissors  cut  away 
a  bit  of  integument  the  size  of  a  half-dime  or  less.  The  end  of  the 
glass  stem  is  drawn  out  in  the  flame  of  a  lamp  to  make  a  suitable  point 
to  the  syringe,  and  this  is  forced  into  the  subcutaneous  tissues,  or  the 
cavity  of  the  abdomen.  The  flame  of  a  small  alcohol  lamp  is  now 
cautiously  applied  to  the  bulb,  and  the  liquid  is  forced  out  by  the  ex- 
pansion of  the  contained  air. 

(/)   EXAMINATION   OF   TISSUES   PEESERVED   IN   ALCOHOL. 

As  the  liver  is  the  organ  which,  m  the  disease  under  investigation, 
shows  the  most  constant  pathological  changes,  I  have  preserved  por- 
tions of  this  organ  in  alcohol  for  future  study  at  nearly  all  of  my  autop- 
sies. I  have  also  preserved  in  the  same  way  portions  of  the  kidney  in 
a  considerable  number  of  cases,  and  of  the  spleen,  intestine,  stomach, 
and  glands  from  the  mesentery  in  a  sufficient  number  of  cases  to  enable 
me  to  study  these  tissues  with  reference  to  pathological  changes  and 
the  presence  of  microorganisms. 

My  thin  sections  of  the  tissues  have  been  made  with  the  most  ap- 
proved modern  microtomes,  and  have  been  stained  seeundem  artem  by 
various  methods.  The  staining  reagent  most  extensively  employed  has 
been  the  alkaline  solution  of  methylene  blue  made  according  to  Loef- 
fler's  formula.  I  have  also  stained  manj^  sections  with  cabol-fuchsin  so- 
lution, with  aniline-oil-fuchsin  (tubercle  stain),  by  Gram's  method,  by 
Weigert's  method,  by  the  method  of  Kiihne,  etc. 

(<7)   PHOTOMICROGRAPHS   OF   MICROORGANISMS  ENCOUNTERED. 

I  have  made  photomicrographs  of  the  microorganisms  encountered 
in  my  researches,  both  for  the  purpose  of  illustrating  my  report  and  as 
the  best  method  of  studying  their  morphology  and  comparing  one  with 
another. 

All  bacteriologists  now  recognize  that,  as  a  rule,  it  is  impossible  to 
identify  the  difl'erent  species  of  bacteria  by  their  morphological  charac- 
ters. There  are  a  number  of  distinct  species  of  micrococci,  and  of  ba- 
cilli, which  resemble  each  other  so  closely  in  form  and  dimensions  that 
it  is  impossible  for  experts  to  decide  from  a  microscopical  examination 
alone  whether  they  are  identical  or  not.  This  can  only  be  determined 
by  other  characters,  such  as  growth  in  various  culture  media,  patho- 
genic power,  etc.  But,  on  the  other  hand,  constant  morphological  dif- 
ferences enable  us  to  differentiate  microorganisms  of  this  class,  and 
such  diflerences  are  shown  in  well-made  photomicrographs,  which  en- 
able us  to  promptly  recognize  differences  of  form,  of  dimensions,  and  of 


no 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


arrangement.  Measurements  are  also  made  with  great  ease  when  such 
photomicrographs  Lave  been  made  with  a  standard  amplification.  In 
those  which  I  have  made  the  amplification  has  usually  been  exactly 
1,000  diameters.  They  have  been  made  with  the  apochromatic  objec- 
tives and  projection  eyepieces  of  Zeiss,  and  the  amplification  has  been 
determined  by  projecting  upon  the  screen  the  ruled  lines  upon  a  stage 
micrometer  made  for  me  by  Professor  Kogers  of  Cambridge. 

My  photomicrographs  have  mostly  been  made  from  fuchsin-stained 
preparations,  and  have  required  the  use  of  orthochromatic  plates  and 
a  yellow  screen. 

The  screen  which  I  have  used  is  made  by  adding  an  alcoholic  solu- 
tion of  tropolin  to  a  strong  solution  of  gelatine,  boiling  to  remove  the 
alcohol,  and  then  pouring  the  gelatine  upon  a  glass  plate,  where  it  is 
allowed  to  dry.  By  means  of  Canada  balsam  another  glass  plate  is 
cemented  to  the  one  having  the  stained  gelatine  coating  to  prevent 
this  from  being  scratched. 

Some  of  my  photomicrographs  have  been  made  by  means  of  the 
calcium  light,  but  the  greater  number  have  been  made  by  gaslight, 
which  has  a  decided  advantage  over  any  other  artificial  light  known  to 
me  ou  the  score  of  convenience  and  economy.  I  prefer  sunlight  and 
the  use  of  a  heliostat,  on  account  of  the  shorter  exposures,  but  an 
extended  experience  has  shown  me  that  there  are  many  disappoint- 
ments when  one  depends  on  the  light  of  the  sun.  On  the  day  we  have 
selected  for  making  our  i)hotomicrographs  it  may  be  obscured  by 
clouds,  and  often  for  weeks  together  there  will  be  no  day  suitable  for 
our  purpose. 

My  apparatus  for  making  photomicrographs  by  gaslight  is  shown 
in  Fig.  5 ;  a  is  the  camera,  which  has  a  pyramidal  bellows  front,  sup- 


ri5. 5. 


Ijorted  by  the  heavy  block  of  w;ood  b;  this  can  be  pushed  back  upon 
the  baseboard  which  supports  it,  so  as  to  allow  the  operator  to  place 
his  eye  at  the  eyepiece  of  the  microscope.  When  it  is  brought  forward 
an  aperture  of  proper  size  admits  the  outer  extremity  of  the  eyepiece 
and  shuts  out  all  light  except  that  coming  through  the  objective;  c  is 
the  microscope,  d  the  Abbe  condenser  supported  upon  a  substage;  eis 
a  thick  asbestus  screen  for  protecting  the  microscope  from  the  heat 
given  off  by  the  battery  of  gas-burners  /.  This  asbestus  screen  has  an 
aperture  of  proper  dimensions  to  admit  the  light  to  the  condenser  d. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  Ill 

The  gas  burners  are  arranged  in  a  series  witb  the  i3at  portion  of  the 
flame  facing  the  aperture  in  the  asbestus  screen  e.  The  concave 
metallic  mirror  g  is  properly  phiced  to  reflect  the  light  in  the  desired 
direction.  I  have  not  found  any  advantage  in  the  use  of  a  condensing 
lens  other  than  the  Abbe  condenser  upon  the  substage  of  the  micro- 
scope. With  Carbutt's  orthocbromatic  plates,  sensitometcr  23,  and  a 
3'ellow  screen  back  of  the  Abbe  condenser,  I  have  found  that  an  ex- 
posure of  from  10  to  15  minutes  is  required  when  the  screen  is  in  proper 
position  to  give  an  amplification  of  1,000  diameters  with  the  apochro- 
matic  objective  of  Zeiss,  ol.  im.,  3mm.,  ap.  1.30,  and  his  projection  eye- 
l)iece  No.  3. 

My  arrangement  for  focusing  is  also  shown  in  the  figure.  The  brass 
rod  i  has  at  one  extremit}'  tlie  grooved  wheel  h,  which  is  connected  with 
the  fine- adjustment  screw  of  the  microscope  by  meaus  of  a  cord.  The 
focusing  wheel  J  may  be  slipped  along  the  rod  i  to  any  desired  position, 
and  is  retained  in  place  by  a  set  screw.  The  rod  i  is  supported  above 
the  camera  by  arms  depending  from  the  celling  or  attached  to  the  base- 
board supi)orting  the  camera,  at  such  a  height  that  the  focusing  wheel 
j  may  be  easily  reached  with  the  right  hand  when  the  oi)erator  has  his 
eye  at  the  center  of  the  focusing  screen. 


ly-GENHRAL  RESULTS  OF  INVESTIGATIONS  MADE. 

(«)   EXAMINATION   OF   "  SMEAR- PEJEPARATIONS." 

As  stated  under  the  heading  "  Methods  of  l^esearch,"  I  have  made 
•smear  preparations  from  the  material  obtained  at  my  autopsies  in  the 
■entire  series  of  cases.  These  have  for  the  most  part  been  stained  with 
an  aqueous  solution  of  fuchsin. 

My  preparations  of  blood  from  the  heart  have  not  shown  the  presence 
of  microorganisms  even  in  cases  in  which  I  have  obtained  them  by  the 
•culture  method.  This  is  easily  explained.  When  I  add  two  or  three 
drops  of  blood  to  liqueiied  flesh-peptone-gelatine  in  a  test  tube  and  make 
■an  Esmarch  roll-tube,  every  microorganism  present,  capable  of  growing 
in  this  medium,  forms  a  colony.  Now,  as  a  rule,  the  result  of  such  cul- 
tures has  been  negative,  but  in  certain  cases  colonies  of  the  bacterium 
coli  commune,  and  occasionally  of  other  bacilli,  have  been  develoiied  in 
these  cultures.  But  the  number  of  colonies  has  been  comparatively 
small,  and  the  solitary  and  scattered  bacilli  which  produced  them  might 
easily  escape  attention  in  a  smear  preparation,  for  the  amount  of  blood 
used  in  my  culture  experiments  would  make  very  many  of  these.  The 
same  remark  applies  to  similar  preparations  made  from  the  tissues,  but 
here  the  result  is  somewhat  diflerent,  inasmuch  as  in  a  certain  propor- 
tion of  the  cases  microorganisms  have  been  found  in  my  examination  of 
smear  preparations  from  the  liver,  made  as  soon  as  possible  after  the 
autopsy. 

This  is  shown  by  the  following  notes,  which  I  transcribe  from  my 
note  books: 

Autopsy  Ko.  14,  Case  1,  1889. — "Direct  examination  of  material  from  liver  aud  kidney 

shows  the  presence  of  a  large  bacillus  with  square  ends."     (My  bacillus  N.) 
Autopsy  No.  18,  Case  5,  1889.—"  Direci  examination  of  blood  negative,  of  liver  a  few 

small,  oval  bacilli  in  pairs." 
Autopsy  No.  22,  Case  9,  1889. — "Bacilli  in  liver  on  direct  examination." 
Autopsy  No.  28,  Case  15,  1889. — "  Material  from  liver,  in  collecting  bulb,  9  bours  after 

collection,  contains  a  large  bacillus.     Slide  1325." 
Autopsy  No.  29,  Case  16,  1889.—  "  Numerous  bacilli  in  liver  on  direct  examination  («). 

They  are  in  groups.     Slide  1368." 
Autopsy  No.  33,  Case  20, 1889. — "  Bacillus  Npresent  in  liver  at  time  of  making  autopsy. 

Slide  1426." 
Autopsy  No.  39,  Case  26,  1889.— "  Bacillus  N  in  liver.     Slide  1469." 
Autopsy  No.  41,  Case  28, 1889. — "  Liver  contains  a  few  large  bacilli  (N).     Slide  147G." 

As  was  to  have  been  expected,  my  suiear  prepaiations  made  from 
material  obtained  from  the  stomach  aud  intestine  have  always  shown 

112 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  113 

the  abundant  presence  of  microorganisms.  As  in  material  from  the 
same  source  obtained  from  persons  dying  from  other  diseases  than 
yellow  fever,  or  from  accident,  the  microorganisms  present  in  the  ali- 
mentary canal  are  various  and  differ  to  some  extent  in  difterent  indi- 
viduals. There  is  no  single  one  to  fix  the  attention  as  being  j)eculiar 
to  yellow  fever,  or  so  constantly  and  abundantly  present  as  to  give 
ground  to  the  belief  that  it  is  concerned  in  the  etiology  of  this  disease. 

In  the  contents  of  the  stomach  one  finds  micrococci  and  bacilli  of 
various  forms  and  very  commonly  numerous  cells  of  a  torula,  resembling 
in  its  morphology  torula  cerivisece. 

The  micrococci  resemble  those  constantly  found  in  the  healthy  human 
mouth.  Some  are  in  irregular  groups,  some  in  long  chains,  and  some  in 
sarcina-like  groups ;  but  no  one  form  is  constant.  The  bacilli  also  differ 
greatly  in  morphology.  .  In  one  case  short  oval  bacilli  in  chains  were 
exceedingly  abundant;  in  other  cases  bacilli  resembling  the  colon  bacil- 
lus, or  larger  bacilli  in  chains,  were  the  most  prominent  forms  present.  In 
the  intestine  micrococci  are  not  so  frequently  encountered,  and  short  oval 
bacilli  resembling  the  bacterium  coli  commune  or  larger  bacilli  resembling 
my  bacillus  IST  are  more  abundant.  Evidently  no  conclusions  of  any 
value  could  be  reached  by  a  microscopical  examination  of  these  various 
organisms  without  resorting  to  culture  experiments,  by  which  they  may 
be  isolated  and  studied  separately.  This  is  the  difficult  task  which  I 
felt  compelled  to  undertake  and  the  results  of  which  will  be  given  un- 
der another  heading.  But  I  may  remark  here  that  I  have  not  obtained 
in  my  cultures  nearly  all  of  the  forms  which  I  have  recognized  in  my 
smear  preparations  from  the  stomach  and  intestine.  Some  of  these  I 
did  not  obtain  at  fiist  because  I  made  only  aerobic  cultures  and  they 
prove  to  be  "  strict  auaerobics."  Others  have  not  developed  even  in  my 
anaerobic  cultures,  and  the  inference  is  that  the  media  employed  may 
not  be  suitable  for  their  growth.  It  is  quite  pos.^ible  that  certain  of  the 
bacteria  of  the  intestine  depend  for  their  development  upon  some  of  the 
excretory  products  peculiar  to  this  locality,  or  upon  the  presence  of  other 
species  which  evolve  products  necessary  for  their  growth. 

I  have  had  my  attention  especially  attracted  by  an  extremely  slender 
and  long  bacillus  which  has  been  very  abundant  in  many  of  the  smear 
pieparations,  but  wliich  has  never  shown  itself  in  my  cultures.  It  is 
the  smallest  microorganism,  so  far  as  its  breadth  is  concerned,  that  I 
have  yet  encountered ;  is  a  flexible  filament  as  shown  by  the  various 
shapes  it  assumes,  and  may  reach  a  length  of  50  micromillimetres  or 
more. 

[h)   AiilPtOBIC    CULTURES. 

My  aerobic  cultures  from  blood  drawn  from  one  of  the  cavities  of  the 
heart  in  one  of  the  collecting  bulbs  described  have  in  a  majority  of  the 
cases  given  a  negative  result;  but  in  a  certain  proportion  of  the  cases 
colonies  have  developed  in  Esmarch  roll-tubes  to  which  one  or  more 
drops  of  blood  had  been  added. 
4UG7 8 


114     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

My  first  five  autopsies,  made  in  1SS8,  gave  a  negative  result.  In  case 
C,  autopsj"  4  hours  after  death,  colonies  of  two  dillerent  kinds  were  ob- 
tained in  cultures  from  the  blood,  liver,  and  kidney.  One  of  these  was 
my  bacillus  a  [bacterium  coll  commune). 

Again,  in  cases  7  and  S  the  result  was  negative;  but  in  case  9,  in  which 
the  autopsy  was  made  5  hours  after  death,  numerous  colonies  of  bacillus 
a  developed  in  my  cultures  from  the  blood,  liver,  and  kidney.  The  next 
case  in  which  I  obtained  microorganisms  from  the  blood  was  No.  15, 
Havana,  1889.  In  this  case  a  few  colonies  of  a  diflerent  bacillus  were 
found. 

In  case  18, 1  again  obtained  a  few  colonies  of  bacillus  a. 

Case  19  gave  a  negative  result,  and  in  subsequent  autopsies  I  did  not 
collect  blood  from  the  heart,  inasmuch  as  the  material  obtained  from 
the  liver  always  contained  a  considerable  quantity  of  blood,  and  would 
show  the  presence  of  microorganisms  if  they  were  to  be  found  in  the 
general  circulation. 

The  results  obtained  in  my  aerobic  cultures  from  the  liver  and  kid- 
ney are  as  follows : 

In  case  1,  I  obtained  a  single  colony  of  bacillus  a  in  my  culture  from 
the  kidney.  The  same  bacillus  was  obtained  from  the  kidney  of  case  3, 
and  in  case  5;  the  cultures  from  case  6  gave  the  same  bacillus  in  gela- 
tine Esmarch  tubes  from  the  liver  and  kidney,  associated  with  another 
bacillus  not  particularly  described  in  my  notes.  In  case  9,  I  obtained 
numerous  colonies  of  bacillus  a  in  cultures  from  the  blood,  liver,  and 
kidney.  In  case  14,  a  few  small  transparent  colonies  developed  in  my 
culture  from  the  liver,  a  few  colonies  of  a  micrococcus  were  obtained 
from  the  spleen,  and  my  bacillus  g  was  obtained  from  the  spleen  and 
kidney.  In  case  16  numerous  colonies  of  a  bacillus  designated  by  the 
letter  p,  which  I  now  believe  to  be  identical  with  m^'  bacillus  x,  were 
obtained  in  my  gelatine  Esmarch  tubes  from  the  liver  and  kidney.  This 
autopsy  was  a  late  one,  having  been  made  13i  hours  after  death.  In 
case  18  a  few  colonies  of  bacillus  x  were  obtained  from  the  kidney.  In 
case  20  the  colon  bacillus  («)  was  obtained  from  theli\"er ;  in  case  28,  my 
cultures  from  the  liver  contained  a  liquefying  bacillus.  In  case  29  cul- 
tures from  the  liver  contained  bacillus  a  and  bacillus  x.  In  case  30 
cultures  from  the  liver  contained  numerous  colonies  of  bacillus  a  and 
of  bacillus  x.  In  case  33  numerous  colonies  of  bacillus  a  were  obtained 
in  gelatine  Esmarch  tubes  from  the  liver. 

A  summary  of  these  results  shows  that  I  have  obtained  microorgan- 
isms in  my  aerobic  cultures  as  follows :  In  blood  from  the  heart,  4  times 
in  19  cases;  in  the  liver  or  kidney  or  both,  13  times  in  43  cases. 

It  will  be  noticed  that  the  microorganisms  most  frequently  encountered 
were  non-liquefying  bacilli,  mj^  bacillus  a  and  bacillus  x. 

We  are  therefore  able  to  assert  in  the  most  positive  manner  that  the 
blood  and  tissues  of  yellow  fever  cadavers  do  not  contain  aiirobic  liquefy- 
ing organisms,  uidess  by  rare  exception,  and  can  definitely  exclude  the 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  115 

micrococcus  of  Freire  and  the  tetragenns  of  Finlay  from  consideration 
as  possible  agents  in  the  etiology  of  this  disease,  as  both  of  these  grow 
readily  in  the  culture  medium  used  in  these  investigations  and  both 
liquefy'  gelatine. 

The  non-liquefying  bacilli  found  in  a  certain  proportion  of  the  cases 
are  not  in  sufficient  numbers  or  sufficiently  constant  to  give  support  to 
the  view  that  they  are  the  specific  cause  of  the  disease,  and  the  fact 
that  they  are  not  found  in  a  considerable  number  of  typical  cases  is 
sufficient  reason  for  excluding  them  as  being  directly  concerned  in  its 
etiolog}"  by  reason  of  their  presence  in  the  blood  and  tissues.  But  we 
may  suppose  that  they  have  their  proper  habitat  in  the  alimentary  canal 
and  that  the  morbid  phenomena  are  due  to  a  toxic  ptomaine,  produced 
in  this  situation.  Under  this  hypothesis  the  occasional  i)rescnce  of 
these  bacilli  in  the  tissues  is  to  be  regarded  as  accidental  and  as  result- 
ing from  the  emigration,  during  the  last  hours  of  life  or  post-mortem, 
of  microorganisms  from  the  intestine,  and  we  have  to  ascertain  whether 
one  of  the  bacilli  found  most  commonly  in  tlie  tissues  or  any  other 
microorganism  present  in  the  alimentary  canal  is  the  specific  agent  we 
are  in  search  of. 

AEROBIC   CL'LTDEES   TROJI   THK   STOMACH   AXD   IXTESTINE, 

As  heretofore  stated,  direct  examination  of  stained  preparations  from 
the  stomach  and  intestine  reveals -^the  presence  of  a  vast  number  and 
great  variety  of  bacteria.  But  our  aerobic  cultures  do  not  enable  us  to 
isolate  all  of  the  different  forms  which  we  may  recognize  by  direct  ex- 
amination. A  complete  bacteriological  analysis  of  the  intestinal  con- 
tents involves  an  amount  of  labor  that  none  but  experts  in  this  line  of 
research  are  likely  to  comprehend ;  and  as  very  many  of  the  micro- 
organisms found  in  this  situation  will  not  grow  in  the  presence  of  oxy- 
gen, both  aerobic  and  anaerobic  cultures  must  be  made  in  a  variety  of 
media.  Moreover,  our  methods  give  us  only  those  organisms  which 
are  most  abundantly  present,  for  these  alone  remain  in  the  third  of  a 
series  of  plate-cultures,  or  Esmarch  roll-tubes,  in  which  we  expect  to 
obtain  isolated  colonies.  In  the  case  of  non-liquefying  organisms,  es- 
pecially, we  have  no  means  of  knowing  how  many  species  present  in 
No.  1  of  a  series  of  Esmarch  roll-tubes  have  been  left  behind  in  the 
diluting  iDrocess  by  which  we  obtain  isolated  colonies  in  tube  ISTo.  3. 
The  presence  of  liquefying  microorganisms,  when  these  are  few  in 
number,  is,  however,  revealed  in  No.  1  of  a  series,  although  the  liquefy- 
ing center  may  include  a  variety  of  microorganisms,  and  it  is  only  by 
making  a  second,  and  often  a  third,  series  of  roll-tubes,  that  we  are 
able  to  obtain  the  liquefying  organism  in  pure  cultures. 

I  may  say,  in  general,  with  reference  to  my  cultures  from  material 
obtained  from  the  stomach,  and  intestine  post-mortem,  and  from  the 
alvine  discharges  during  life,  thathy  far  the  greaternujuber  of  the  micro- 
organisms present  do  not  liquefy  gelatine.     In  a  series  of  Esmarch  roll- 


116  ETIOLOGY    AND    PllEVENTION    OF    YELLOW    FEVER. 

tubes,  ISTo.  1  is  sometimes  comiiletely  liquefied  in  24  hours,  No.  2  may 
contain  a  number  of  liquefying?  colonies,  but  JVo.  3  almost  without  excep- 
tion contains  isolated  colonies  of  non-liquefying  hacilli.  In  a  considerable 
proportion  of  the  cases  tbere  are  no  liquefying  colonies  even  in  tube  No. 
1  of  a  series,  in  which  the  non-liquefying  colonies  are  so  numerous  as  to 
give  the  entire  gelatine  coating  of  the  tube  an  opalescent  appearance, 
due  to  the  closely  crowded  minute  colonies.  This  fact  seems  to  exclude 
from  consideration  the  supposition  that  yellow  fever  is  due  to  the  pres- 
ence in  the  alimentary  canal  of  a  liquefying  bacillus,  as  is  the  case  in 
cholera. 

We  might  be  satisfied  with  this  general  statement  but  for  the 
fact  that  Dr.  Paul  Gibier,  a  French  bacteriologist,  during  his  visit  to 
Havana  in  1888,  encountered  a  liquefying  bacillus  which  he  supposed, 
for  a  time  at  least,  to  be  the  specific  microbe  of  the  disease.  In  view 
of  Dr.  Gibier's  publication  referring  to  this  bacillus,  I  have  given  special 
attention  to  a  search  for  liquefying  bacilli  in  the  alimentary  canal  and 
in  the  dejecta.  As  stated,  no  liquefying  colonies  have  made  their  ap- 
pearance in  a  considerable  proportion  of  the  cases,  but  in  a  few  excep- 
tional cases  the  liquefying  colonies  have  been  very  numerous.  Thus  in 
case  2,  Havana,  1888,  my  bacillus  e  was  present  in  my  cultures  from 
the  stomach.  In  case  4  and  in  case  9,  Gibier's  bacillus  (my  bacillus  g) 
was  obtained  in  my  cultures  from  the  stomach  and  intestine.  In  case 
10  my  note  is,  "  single  liquefying  colonj'  from  stomach  (Gibier  ?)."  Case 
11,  which  was  an  autops}^  made  1  hour  after  death,  on  the  evening  of 
my  arrival  at  Decatur,  Ala.  (October  3,  1888),  gave  me  very  numerous 
liquefying  colonies,  both  from  the  stomach  and  the  intestine,  and  the 
liquefying  organism  turned  out  to  be  the  Staphylococcus  pyogenes  aureus. 

In  my  second  autopsy  at  Decatur  (case  12)  I  again  obtained  numerous 
liquefying  colonies  in  my  gelatine  Esmarch  tubes  from  the  stomach  and 
intestine,  but  this  was  a  very  different  organism  from  that  encountered 
in  the  preceding  case  ;  it  proved  to  be  a  large  bacillus  with  square  ends 
of  the  "subtilis"  order  (my  bacillus  q).  In  a  third  autopsy,  made  at 
Decatur,  no  liquefying  colonies  were  found  in  my  cultures  from  the 
stomach  and  intestine  (case  13).  My  notes  with  regard  to  this  point 
in  the  autopsies  made  at  Havana  in  1889  are  as  follows : 

No. 14.  "No  liquefying  colonies  from  stomach  or  intestine."  No.  15.  "  No  liquefying 
colcmies  in  cultures  from  intestine  ;  a  few  in  Esmarch  No.  1  from  stomach."  No.  16. 
"  Liquefying  bacillus  (bac.  o)  in  gelatine  Esmarch  tubes  from  stomach  and  intestine." 
No.  17.  "  Cultures  from  intestine  bacillus  a  and  a  single  liquefying  colony,  not  Gibier's 
bac."  No.  19.  "  No  liquefying  colonies  from  stomach  or  intestine  at  end  of  24  hours." 
No.  20.  "  Bacillus  (/,  obtained  from  intestine.  Esmarch's  1  and2,  both  liquefied  at  end 
of  24  hours."  No.  21.  "  Gelatine  Esmarch  No.  1  from  intestine  liquefied  at  end  of  48 
hours,  bac.  ee."  No  remarks  in  cases  22,  23,  and  24.  No.  25.  "  No  liquefaction  of  gela- 
tine Esmarch  tubes  from  intestine."  No.  27.  "  Liquefying  bacillus  in  gel.  Es.  from  in- 
testine." Tube  No.  1  liquefied  at  end  of  24  hours."  No.  28.  "No  lique  lying  colonies  in 
gel.  roll-tubes  from  intestine."  No.  29.  "Gelatine Esmarch  No.  1,  from  iutestine  lique- 
fied in  24  hours,  single  liquefying  colony  in  No.  2,  numerous  non-liquefying  colonies 
in  No.  3,  colon,  etc."     Later  note:  "The  liquefying  bacillus  from  intestine  is  g." 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  117 

No  30,  "No  liquefaction  of  gelatiue  Esmarch  No.  1  in  48  hours;  No.  3  contains  nn- 
nierous  colonies  of  bacillus  x."  No.  31.  "  No  liquefaction  of  gelatine  tubes  from  in- 
testine at  end  of  48  hours.  No.  3  contains  mostly  colon  bacillus.  No.  32.  "No  lique- 
faction of  gelatine  Esmarch  No.  1  from  intestine  in  48  hours."  No.  33.  Esmarch  No. 
1,  from  intestine,  contains  some  liquefying  colonies  at  end  of  48  hours  (bac.  g.)  ;  none 
in  No.  2  and  3,  which  contain  numerous  colonies  of  the  colon  bacillus.  No.  35.  "A 
few  liquefying  colonies  in  Esmarch  No.  1  from  intestine."  No.  36.  "  No  liquefying 
colonies  in  Esm.irch  1  from  intestine."  No.  37.  "About  100  liquefying  colonies  in  Es- 
march No.  1  from  intestine ;  none  in  2  and  3,  which  contain  colon  bacillus  and  bacil- 
lus X."    No.  38.  Six  liquefying  colonies  in  Es.  1  from  intestine  ;  none  in  2  and  3. 

It  will  be  seen  irom  these  notes  that  Gibier's  bacillus  (my  bacillus  g) 
has  been  present  in  the  intestine  in  a  few  of  my  cases,  but  that  it  has 
been  absent  in  a  much  greater  number,  and  when  present  has  not  been 
abundant  as  compared  with  the  non-liquefying  organisms.  The  infer- 
ence is  that  its  presence  is  accidental,  and  that  it  bears  no  etiological 
relation  to  the  disease,  and  in  view  of  the  facts  developed  by  my  culture 
experiments,  the  broad  statement  seems  justified  that  yellow  fever  is  not 
due  to  a  liquefying  aerohic  bacillus. 

One  reservation  might,  perhaps,  be  made  before  this  general  state- 
ment will  be  accepted.  May  not  the  bacillus  of  Gibier  or  some  other 
liquefying  bacillus  be  present  in  the  intestine  during  the  earlier  stages 
of  the  disease  and  disappear  later,  so  that  it  is  not  found  as  a  constant 
thing  in  material  obtained  from  the  intestine  post-mortem  I 

Dr.  Gibier  himself  has  made  the  suggestion,  and  my  researches  in 
Decatur  were  largelj^  made  for  the  purpose  of  obtaining  a  definite  an- 
swer to  this  question.  These  researches  show  that  liquefying  bacilli 
were  encountered  rather  more  frequently  in  cultures  from  the  alvine 
discharges  of  yellow  fever  patients  than  in  those  from  the  intestinal 
contents  obtained  post-mortem.  But  the  bacillus  obtained  most  fre- 
quently was  not  that  of  Gibier,  but  my  bacillus  o.  The  remarks  made 
with  reference  to  the  comparative  abundance  of  liquefying  organisms 
in  material  obtained  from  the  intestine  post-mortem  apply  as  well  to 
the  dejecta  during  life,  as  compared  with  the  non-liquefying  organisms 
they  are  very  infrequent.  This  is  shown  by  the  following  notes  made 
in  Decatur : 

Feces,  case  1 :  "Esmarch  tubes  contain  in  great  abundance  the  colon  bacillus,  and 
in  much  smaller  numbers  a  liquefying  bacillus,  o."  Feces,  case  2:  "Esmarch  No.  1 
contains  a  liquefying  bacillus,  same  as  in  case  1,  not  very  numerous,  as  shown  by  ab- 
sence from  tubes  2  and  3."  Feces,  case  3 :  "  Colon  bacillus  the  principal  form;  a  few 
liquefying  colonies  in  Esmarch  No.  1."  Feces,  case  4:  "  Liquefying  bacillus  in  tube 
1,  and  a  few  colonies  in  tube  2;  bacillus  </."  Feces,  case  5:  "Liquefying  bacillus  in 
tube  1,  colon  bacillus  in  tubes  2  and  3  (single  liquefying  colony  in  tube  2)."  Feces, 
case  6:  "  Liquefying  colonies  in  tube  1  (bacillus  g),  colon  bacillus  in  tubes  2  and  3, 
single  liquefying  colony  in  tube  2."  Feces,  No.  7:  "No  liquefying  colonies;  a  doubt- 
ful case."  Feces,  case  8 :  "Numerous  liquefying  colonies  in  tube  1 ;  bacillus  o."  Feces, 
case  9 :  "Several  liquefying  colonies  in  tube  1."  Feces,  case  10 :  "  No  liquefying  col- 
onies at  end  of  48  hours;  liquefaction  of  tube  1  at  end  of  3  days."  Feces,  case  11: 
"Tubes  1  and  2  both  liquefied  at  end  of  48  hours."  Feces,  case  12  :  "Tubes  1  and  2 
both  liquefied  at  end  of  48  hours."  Feces,  case  13:  "Tabes  1  and  2  both  liquefied  at 
end  of  48  hours."     Feces,  case  14 :  "No  liquefying  colonies  at  end  of  48  hours."    Feces, 


118     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

case  15:  "Tubes  1  and  2  liquelied  at  eiul  of  48  honrs."  Feces,  case  16:  "Tnbel 
partly  liquefied  at  end  of  48  hours."  Feces,  case  17:  "  Numerous  liquefying  colonies 
in  tube  1 ;  bacillus  o."  Feces,  case  18:  "Both  tubes  liquefied  at  eud  of  48  hours." 
Feces,  case  19 :  "Tube  1  partially  liquefied  in  48  hours;  tube2not;  bacillus  o."  Feces, 
case  20:  "Tube  1  liquefied  in  24  hours;  no  liquefying  colonies  in  tube  2."  Feces,  case 
21:  "Numerous  liquefying  colonies  in  48  honrs;  bacillus  o  and  bacillus  e."  Feces, 
case  22:  "Tube  1  liquelied."  Feces,  case 23 :  "Tube  1  liquefied  ;  tube  2  not."  Feces, 
case  24  :  "Tube  1  liquefied  in  24  hours;  a  few  colonies  in  tube  2  ;  bacillus  o  and  bacil- 
lus e."  Feces,  case  25  :  "Both  tubes  liquefied  at  end  of  24  honrs;  bacilluso."  Feces, 
case  26:  "Tube  1  liquefied  in  24  hours;  tube  2  about  20  colonies;  o  and  t."  Feces, 
27:  "Tube  1  completely  liquefied  in  24  hours;  No.  2,  20  to  30  colonies."  Feces,  case 
28:  "  Tube  1  liquefied  in  24  hours  ;  no  liquefying  colonies  in  tube  2;  bacilluso."  Feces, 
case  29:  "Tube  1  liquelied  in  24  hours;  single  colony  in  tube  2."  Feces,  case  30 : 
"No  liquefaction  in  either  tube."  Feces,  case  31 :  "Tube  1  completely  liquefied  in 
24  hours ;  bacillus  t,  and  another,  not  o  or  ^ ;  tube  2  no  liquefaction."  Feces,  case  32 : 
"No  liquefiiction  in  24  hours;  tube  1  liquefied  in  48  hours."  Feces,  case  33 :  "Tube 
1  liquefied  in  24  hours;  all  three  tubes  liquefied  in  48  hours;  bacillus^."  Feces,  case 
34:  "Tube  1  not  liquefied  in  48  hours;  some  liquefaction  on  third  day ;  bacilluso." 
Feces,  case  35 :  "  No  liquefaction  in  3  days."  Feces,  case  36:  "A  few  liquefying  col- 
onies in  tube  1."  Feces,  case  37 :  "  Tube  1  contains  a  few  liquefying  colonies;  bacil- 
lus 0." 

It  will  be  noticed  that  iu  many  instances  Ihave  simply  noted  the  fact 
that  liquefaction  of  tube  1  occurred  in  48  hours,  etc.,  without  specifying 
the  liquefying  organism.  This  was  because  I  had  neither  time  nor  cul- 
ture material  to  determine  this  in  every  case.  The  general  result  of 
my  culture  experiments  is  that  liquefying  organisms  are  present  in  the 
dejecta  in  comparatively  small  numbers,  and  that  there  is  no  one  which 
is  constant,  but  that  liquefaction  of  the  gelatine  is  due  sometimes  to 
one  and  sometimes  to  another  organism  of  this  class. 

In  a  series  of  comparative  experiments  made  upon  the  alvine  dis- 
charges of  convalescents  and  healthy  persons  liquefying  colonies  ap- 
peared somewhat  less  frequently,  as  is  shown  by  the  following  notes : 

Octoher  25;  Feces,  self.  "A  single  liquefying  colony  iu  tube  1."  October  25  :  Feces 
of  convalescents  of  3  weeks.  "  No  liquefying  colonies."  October  26:  Feces  of  healthy 
man.  "  No  liquefying  colonies."  October  27:  Feces,  healthy  man.  "  Neutral  reac- 
tion; completely  liquefied  in  3  days."  October  27:  Feces  of  convalescent.  "About 
20  liquefying  colonies."  October  28  :  Feces,  healthy  man.  "Completely  liquefied  on 
third  day."  October  28:  Feces  of  convalescent.  "Tube  1  completely  liquefied  in  24 
hours;  tube  2  on  third  day."  October  28:  Fecrs,  healthy  man.  "  Not  liquefied." 
October  28:  Feces,  healthy  man.  "  Completely  liquefied  on  third  day."  October  28: 
Feces,  healthy  man.  "No  liquefying  colonies."  October  29:  Feces,  convalescent. 
"  Single  liquefying  colonies."  October  29  :  Feces,  convalescent.  "Completely  lique- 
fied in  48  hours."  November  26:  Feces,  convalescent.  "Tube  1  liquefied;  bacillus 
e."  November  26:  Feces,  healthy  man.  "  Tube  1  liquefied  in  48  hours;  a  few  lique- 
fying colonies  in  tube  2;  bacillus  e."  November  25:  Feces,  healthy  man.  "Tube  1 
liquefied  in  48  hours;  some  liquefying  colonies  in  tube  2;  Wurtzel  bacillus."  Novem- 
ber 26:  Feces,  healthy  man.  "Tube  1  liquefied  in  48  hours,  some  liquefying  colonies 
iu  tubes  2  and  3."  November  26:  Feces,  convalescent.  "Tubes  1  and  2  liquefied  and 
a  few  colonies  in  tube  3." 

It  must  be  remembered  that  in  all  these  experiments  a  considerable 
amount  of  material  is  added  to  tube  No.  1,  usually  2  or  3  drops  from 


ETlOtOGY    AND    PREVENTION    OP    YELLOW    PEVER.  119 

the  collecting  bulb,  whereas  a  single  oese  is  carried  over  to  tube  No.  2, 
and  again  from  (his  to  No.  3.  Evidently,  in  view  of  the  facts  stated,  no 
special  significance  can  be  attached  to  the  presence  of  any  one  of  the 
liquefying  organisms  encountered,  and  the  bacillus  of  Gibier  must  take 
its  place,  besides  my  bacillus  o,  and  my  bacillus  e,  as  being  one  of  the 
liquefying  organisms  occasionally  present  in  the  intestinal  contents  of 
yellow  fever  patients. 

Inasmuch  as  nonliquefying  bacilli  are  constantly  present  in  great  num- 
bers, our  investigation  calls  for  a  careful  study  of  this  class  of  organisms, 
and  much  of  my  time  has  been  devoted  to  this  portion  of  the  research. 

As  already  stated,  when  my  cultures  from  the  blood  or  tissues  hav^e 
given  a  positive  result  the  microorganisms  present  have  been  nonliquefy- 
ing bacilli,  and  those  most  frequently  found  have  been  my  bacillus  a 
and  my  bacillus  x.  Both  of  these  have  been  present  in  my  cultures 
from  the  intestinal  contents,  and  I  can  not  doubt  that  this  is  the  source 
from  which  they  made  their  way  into  the  blood.  I  have  identified 
bacillus  a  with  the  bacterium  coli  commune  of  Escherich,  and  it  is  con- 
sequently excluded  as  the  specific  cause  of  yellow  fever.  Bacillus  cc  I 
have  not  obtained  up  to  the  present  time  in  my  comparative  researches, 
and  consequently  regard  it  as  possibly  connected  with  the  etiology  of 
the  disease.  But  I  have  not  been  able  to  obtain  any  satisfactory  experi- 
mental evidence  upon  which  to  base  a  positive  claim  that  this  is  the 
case.  I  have  not  isolated  it  in  a  large  number  of  cases,  but  it  was  not 
until  my  second  visit  to  Havana  that  I  difl'erentiated  it  from  the  colon 
bacillus  {a)  with  which  it  is  associated. 

In  my  first  culture  experiments,  made  in  1S88, 1  was  very  much  puzzled 
by  the  contradictory  results  which  1  obtained  in  inoculating  my  cultures 
into  rabbits  and  guinea  pigs.  I  believe  now  that  the  promptly  fatal  re- 
sults obtained  in  certain  cases  in  which  I  injected  cultures  which  1  sup- 
l)osed  contained  only  baccillus  a  were  due  to  the  presence  also  of  my 
bacillus  X.  The  characters  by  which  these  bacilli  are  to  be  dis- 
tinguished, and  a  detailed  account  of  experiments  made  with  them, will 
be  given  in  a  subsequent  portion  of  this  report,  in  which  also  a  systematic 
account  will  be  given  of  some  other  nonliquefying  bacilli  encountered 
in  association  with  them. 

In  thirteen  of  my  autopsies  I  have  collected  urine  through  the  walls 
of  the  bladder.  My  culture  experiments  with  this  have  given  a  nega- 
tive result  in  ten  cases,  and  in  three  I  have  obtained  microorganisms, 
viz:  In  case  1,  "several  colonies  of  bacillus  a  in  culture  from  urine;" 
in  case  2,  "  the  tubes  from  stomach,  intestine,  urine,  kidney,  and  spleen 
all  contain  numerous  colonies  of  a  liquefying  bacillus"  (my  bacillus  e); 
in  case  9,  "  numerous  colonies  of  bacillus  a  in  cultures  from  blood,  liver, 
urine,  and  kidney." 

(C)    ANAiiROBIC   CULTURES. 

My  method  of  making  anaerobic  cultures  has  already  been  described, 
and  an  account  of  the  various  microorganisms  which  I  have  isolated  by 


120  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

tins  metliod  will  be  given  hereafter.  The  general  result  has  been,  so 
far  as  the  blood  and  tissues  are  concerned,  similar  to  that  obtained  iu 
my  aerobic  cultures.  That  is,  various  microorganisms  have  been  en- 
countered in  the  series  of  cases  in  which  this  method  has  been  applied, 
but  no  one  of  them  has  been  constant,  and  in  a  considerable  proportion 
of  the  cases  the  result  has  been  entirelj^  negative. 

Some  of  the  microorganisms  isolated  iu  my  anaerobic  cultures  are 
identical  with  those  obtained  in  aerobic  cultures  from  the  same  source; 
for  my  bacillus  a,  bacillus  x,  and  other  bacilli  associated  with  them  in 
the  intestine  are  facultative  anaerobics,  and  grow  either  in  the  presence 
or  iu  the  absence  of  oxygen.  But  there  are  also  in  the  intestine,  and 
in  the  tissues  obtained  post  mortem  at  a  considerable  interval  after 
death,  a  number  of  "strict  anaerobic"  bacilli.  Some  of  these  I  have 
isolated  and  shall  describe  hereafter. 

The  following  extracts  from  my  note  book  will  show  the  general  re- 
sults obtained  by  this  method.         ^ 

Case  14,  Havana,  April  23, 1889 :  Soldier  io  military  liospital.  Sick  5  days :  autopsy 
9  hours  after  death.  "Direct  examiuation  of  material  from  liver  aud  kidney  shows 
a  large  bacillus  with  square  ends  (bacillus  N).  Numerous  granular  colonies  iu 
anaerobic  culture  from  liver  (N).  Five  liquefying  colonies  in  anaerobic  culture  from 
kidney." 

Associated  with  my  bacillus  N  iu  the  anaerobic  cultures  from  the  liver  of  this  case 
was  a  microorganism  in  chains,  which  I  was  at  first  disposed  to  regard  as  a  short 
bacillus  and  designated  with  the  letter  o.  This  I  isolated  and  have  still  iu  cultiva- 
tion.    I  now  regard  it  as  a  streptococcus. 

Case  15,  April  28,  1889:  Sick  10  days;  autopsy  9  hours  after  death.  "No  micro- 
organisms on  direct  examination  of  material  from  liver  and  kidney.  No  development 
in  aerobic  or  anaerobic  Esmarch  tubesjrom  liver  and  kidney."  Case  16:  Sick  7  days; 
autopsy  13i  hours  after  death.  Numerous  colonies  of  bacillus  x  in  gelatine  cultures 
from  liver  aud  kidney ;  anaerobic  cultures  from  liver  aud  kidney  contain  the  same 
bacillus.  Case  11:  Sick  5  days;  autopsy  5  hours  after  death.  No  colonies  either  in 
aerobic  or  anaerobic  cultures  from  blood,  liver,  kidney  or  urine."  Case  18:  Sick  5 
days;  autopsy  2  hours  after  death.  "Direct  examination  of  blood  negative;  of  liver 
a  few  small  oval  bacilli  in  pairs.  Aerobic  gelatine  Esmarch  tube  from  blood  contains 
a  few  colonies  of  bacillus  a.  Anaerobic  agar  Esmarch  tube  from  blood  contains 
numerous  colonies  of  bacillus  a  and  of  a  short  bacillus  in  chains,  slide  1078.  Anaerobic 
agar  Esmarch  tube  from  kidne\  c  :itains  numerous  colonies;  bacillus  w,  the  same 
from  liver."  Case  19:  "  No  colonies  in  gelatine  Esmarch  tubes  from  blood  or  liver ; 
no  development  in  gelatine  anaerobic  tube  from  blood."  Case  21 :  Sick  seven  days; 
autopsy  10  hours  after  death.  "No  colonies  in  gelatine  Esmarch  tube  from  liver; 
numerous  colonies  of  bacillus  N  in  anaerobic  agar  Esmarch  tube."  Case  24 :  Sick  .5 
days;  autopsy  4^  hours  after  death.  "No  development  in  anaerobic  cultures  from 
liver  aud  kidney."  Case  30 :  "  Aerobic  cultures  from  liver  contain  both  bacillus  a  and 
bacillus  X.  Anaerobic  culture  from  liver  contains  bacillus  N  and  bacillus  O."  Case 
31:  "No  development  in  aerobic  or  anaerobic  cultures  from  liver."  Case  32:  "No 
development  in  aerobic  culture  from  liver,  bacillus  N  in  anaerobic  cultures  from  liver." 
Case  35:  "No  microorganisms  in  liver  on  direct  examination  ;  no  development  in 
aerobic  or  anaerobic  cultures  from  liver."  Case  36 :  "  The  anaerobic  culture  from  the 
liver  in  this  case  gives  numerous  colonies  of  a  facultative  anaerobic  bacillus."  Case 
37 :  No  colonies  in  anaerobic  culture  from  liver.  Case  38  :  "A  few  colonies  of  bacillus 
X  in  anaerobic  culture  from  liver." 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  121 

{d)   RESULTS   OF  EXAMINATION   OF   TISSUES   KEPT  IN  AN   AN'IISEPTIC 

WEAPPING. 

Upon  removing  the  antiseptic  wrapping  from  a  piece  of  liver  or  kid- 
ney preserved  as  heretofore  described,  I  have  usually  found  the  exterior 
of  the  piece  to  he  thoroughly  sterilized  and  free  from  any  signs  of  pu- 
trefactive change.  The  interior,  also,  usually  has  a  fresh  appearance 
and  is  without  any  putrefactive  odor.  But  a  microscopical  examina- 
tion of  a  stained  smear  preparation  shows  that  a  large  number  of  micro- 
organisms are  i)resent,  although  smear  preparations  from  the  same 
material  made  immediately  after  death  have  as  a  rule  given  a  negative 
result.  There  is  evidence  then  that  the  liver  and  the  kidney  of  yellow 
fever  patients  does  contain  microorganisms  when  removed  from  the 
cadaver  at  an  autopsy  made  within  a  few  hours  after  death.  For  the 
numerous  microorganisms  of  various  species  found  in  a  jiiece  preserved 
in  this  way  have  evidently  developed  from  others  which  were  present 
in  small  numbers  at  the  time  it  was  removed  from  the  body.  The 
method  insures  the  destruction  of  any  bacteria  which  njight  acci- 
dentally fall  upon  the  fragment  after  opening  the  cavity  of  the  abdo- 
men ;  and,  as  stated,  the  exterior  of  the  fragment  is  perfectly  preserved 
by  the  antiseptic  wrapi)ing.  Comparative  exijeriments  made  with 
pieces  of  liver  obtained  from  persons  dying  with  other  diseases  have 
given  a  similar  result,  and,  even  in  a  case  of  sudden  death,  in  which  the 
autopsy  was  made  almost  immediately,  I  have  found  numerous  micro- 
organisms. 

The  one  which  I  found  most  constantly  and  most  abundantly  in  yel- 
low-fever tissues  preserved  in  this  way  was  a  large  anaerobic  bacillus — 
my  bacillus  IST.  which  luow callhacillus cadaverinus.  Having  also  found 
this  several  times  in  my  smear  preparations  from  fresh  liver  tissue,  and 
finding  it  to  be  very  common  in  the  contents  of  the  intestine,  I  hoped 
for  a  time  that  it  might  turn  out  to  be  the  specific  infectious  agent  in 
the  disease  under  investigation.  But  before  leaving  Havana,  I  had 
already  found  what  appeared  to  be  the  same  bacillus  in  a  piece  of  liver, 
preserved  in  the  same  way,  which  I  obtained  from  a  case  of  tuberculo- 
sis; and  since  my  return  to  Baltimore  I  have  found  it  in  other  compar- 
ative autopsies;  so  that  I  now  feel  compelled  to  exclude  it  from  consid- 
eration as  having  any  etiological  relation  to  yellow  fever. 

A  number  of  the  bacilli  which  I  have  obtained  from  yellow  fever 
cadavers,  and  shall  hereafter  describe,  have  been  from  pieces  of  liver 
and  kidney  preserved  in  the  manner  mentioned  ;  and  have  been  isolated 
either  directly  by  means  of  Esmarch  roll -tubes,  or  indirectly  by  inocu- 
lations into  guinea-pigs. 

These  bacilli  are  either  strict  or  facultative  anaerobics,  and  they  are 
all  able  to  grow  in  a  decidedly  acid  medium.  Several  of  them  produce 
an  acid  reaction  in  glycerine  agar  tubes,  and  one  (bacillus  i)  produces 
a  very  acid  reaction  in  bouillon  cultures  to  which  5  i)er  cent,  of  glyce- 


122  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

rine  has  been  added.  I  therefore  ascribe  the  very  acid  reaction  of  the 
interior  of  the  piece  of  tissue,  kept  as  indicated,  to  the  presence  of  these 
acid-producing  bacilli.  I  give  below  some  extracts  from  my  notes  re- 
lating to  this  material  kept  in  an  antiseptic  wrapping  for  48  hours : 

Case  1,  Havana,  May  12,  1888:  "May  14,  exauiined  liver  aud  kidnej^kept  in  labora- 
tory for  48  hours.  On  section  there  is  no  putrefactive  odor.  The  kidney  contains  a 
largo  bacillus  with  square  ends — slide  230  ;  the  liver  contains  the  same  bacillus — slide 
231."  Case  18,  May  13,  1889:  "Liver  kept  in  laboratory  43  hours  has  on  cut  surface 
an  intensely  acid  reaction;  kidnej^  also  has  intensely  acid  reaction;  both  contain 
bacillus  N  and  a  small  oval  bacillus  (slide  1081)."  Case  23,  June  A,  1889:  "Liver 
48  hours  iu  laboratory  ;  no  odor,  slightly  acid  reaction,  bacillus  N  not  present."  Case 
28;  "  LiA'er  30  hours  iu  laboratory  contains  bacillus  N  in  large  uumbirs — slide  1336 ;  has 
no  odor  and  an  acid  reaction."  Case  29:  "Liver  48  hours  in  laboratory  has  an  acid 
reaction,  no  odor,  aud  contains  bacilli  resembling  x — slide  1375.  Both  colon  bacillus 
and  bacillus  x  obtained  from  this  liver  kept  48  hours  in  laboratory,  also  bacillus  of 
rabbit  septictpmia  by  inoculations."  Case  30 :  "Liver  48  hours  iu  laboratory  con- 
tains bacillus  N  and  other  bacilli^slide  1414;  acid  reaction."  Case  31:  "LiA'er  48 
hours;  acid  reaction,  bacillus  N — slide  1417."  Case  33  :  "  Liver  48  hours;  bacillus  N, 
acid  reaction,  fresh  appearance."  Case  34:  "Liver  48  hours;  contains  bacillus  N  iu 
small  numbers,  fresh  appearance,  no  odor,  acid — slide  1437."  Case  35:  "Liver  48 
hours;  bacillus  N — slide  1442  ;  very  acid  reaction,  no  odor,  fresh  appearance."  Case 
36:  "Liver  48  hours,  acid,  fresh  appearance,  no  odor,  bacillus  N— slide  1455."  Case 
37:  "Liver  48  hours  in  laboratory  ;  putrefaction  has  commenced  :  various  bacilli  pre- 
sent ;  reaction  faintly  acid."  Case  38:  "  Liver  48  hours  ;  fresh  appearance,  no  odor, 
acid  reaction,  contains  bacillus  N— slide  1468."  Case  39:  "Liver  48  hours,  bacillus 
N."  Case  40:  "Liver  48  hours;  putrefaction  commencing;  various  bacilli  including 
N— slide  1477." 

COMPARATIVE  ATJTOrSIES. 

1^0.  1,  Havana,  May  17,  1889 :  "  Liver  and  kidney  from  case  of  tuberculosis  ;  autopsy 
2  hours  after  death.  May  19,  cut  surface  of  liver  has  a  very  acid  reaction  and  con- 
tains bacillus  N  iu  large  numbers ;  kidney  contains  some  bacillus  in  smaller  numbers  ; 
bacillus  X  not  present." 

No.  2,  Havana,  May  19:  "Autopsy  If  hours  after  death;  tuberculosis;  kidney  at 
end  of  48  hours  fresh  ;  no  microorganisms;  liver,  putrefaction  ;  cut  surf;ice,  acid;  con- 
tains a  large  bacillus  with  round  ends;  bacillus  N  not  present — slide  1120." 

No.  3,  Havana,  May  22:  Case  of  heart  disease.  "Liver  at  the  end  of  48  hours  con- 
tains bacillus  N;  cut  surface  has  a  very  acid  reaction;  bacillus  x  not  present." 

No.  A,  Havana,  May  'Zo:  Abscess  of  liver.  "Autopsy  one-half  hour  after  death.  No 
microorganisms  on  direct  examination  at  end  of  48  hours;  staphylcoccus  obtained  in 
cultures;  cut  surface  of  liver  has  a  slightly  acid  reaction." 

No.  5,  Havana,  May  ^•.  Insane  woman.  "Autopsy  5  hours  after  death;  putrefac- 
tive decomj)osition  of  liver  kept  48  hours  in  antiseiitic  wrapping." 

No.  6,  Havana,  May  30  :  Tuberculosis.  "Autopsy  6  hours  after  death;  bacillusNnot 
present;  slightly  acid  reaction." 

No.  7,  Havana,  June  2:  Heart  disease  ;  autopsy  5  hours  after  death.  "  Liver  jjutrid 
at  end  of  48  hours." 

No.  8,  Baltimore,  Ocioier  30:  Tuberculosis;  autopsy  8  hours  after  death.  "Liver 
preserved  48  hours  in  antiseptic  wrapping  has  a  fresh  appearance,  no  odor,  acid  re- 
action ;  contains  large  bacillus  with  round  ends  and  end  spore — slide  1485." 

Cose  9,  Baltimore,  November  12, 1889 :  Tubercular  meningitis  ;  autopsy  6^  hours  after 
death.  "Liver  kept  for  48  hours  in  laboratory  has  an  acid  reaction  and  onntaius 
various  bacilli ;  one  very  large  with  round  ends,  one  long  aud  slender — slide  1505 ; 
bacillus  N  not  present." 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  123 

Case  10,  November  18,  1889:  Osteomyelitis  of  tibia,  amyloid  liver,  and  kidney. 
"Liver  48  hours  in  laboratorj'  is  perfectly  preserved,  has  a  freph  appcarnnce  and  no 
odor,  very  .acid  reaction.     Contains  nnmerons  and  various  bacilli,  one  resembling  N." 

No.  11:  Tuberculosis;  autopsy  24  hours  after  death.  "Liver  48  hours  in  labora- 
tory very  soft,  and  has  an  empyreumatic  odor;  contains  a  large  bacillus  with  round 
ends;  bacillus  N  not  present." 

Case  12:  Tuberculosis;  autopsy  8  hours  after  death.  Liver  in  oven  at  35°  for  48 
hours;  soft,  liutrefactive  odor;  alkaline  reaction  ;  various  bacilli  present,  N  not  recog- 
nized. 

Case  13 :  Death  from  chloroform  ;  autopsy  at  once.  "  Liver  preserved  in  antiseptic 
wrapping  ;  opened  at  end  of  48  hours  has  an  acid  reaction  and  fresh  appearance  ;  con- 
tains a  large  anaerobic  bacillus  with  end  spores — slide  l.'')43." 

Case  14:  Heart  disease  ;  autopsy  7  hours  after  death.  "  Liver,  48  hours,  fresh  ap- 
peiirance,no  odor,  acid  reaction;  contains  various  bacilli — slide  1.550." 

Case  15  :  Peritonitis  after  laparotomy.  "  Liver  in  antiseptic  wrapping  at  end  of 
48  hours  is  perfectly  fresh  in  appearance,  has  a  very  acid  reaction,  and  contains  large 
anaerobic  bacilli  in  great  numbers  which  appear  to  be  identical  with  my  bacillus  N. 
These  were  not  obtained  in  an  anaerobic  culture  in  glycerine  agar,  but  were  present  in 
an  anaerobic  culture  in  blood  serum  and  glycerine  agar  mixed,  associated  with  other 
bacilli— slide  1898." 

Case  16  :  Tumor  of  uterus ;  autopsy  4hours  after  death.  "  Liver  preserved  48  hours, 
fresh  in  appearance, no  odor,  very  acid  reaction;  various  bacilli;  bacillus N  not  pres- 
ent." 

Tbese  notes  sliow  that  the  large  anaerobic  bacillus  which  I  have 
designated  by  the  letter  IST  was  more  constantly  present  in  the  liver 
from  my  yellow-fever  cases  than  in  my  comparative  autopsies,  but  the 
hope  which  I  entertained  for  a  time  that  it  might  be  the  specific  infec- 
tious agent  has  given  way  before  the  evidence  of  its  presence  in  the 
liver  of  persons  dying  from  other  diseases.  It  is  true  that  I  had  this 
evidence  before  returning  from  Havana,  but  I  admitted  to  myself  the 
possibility  that  acclimated  persons  dying  in  the  infected  city  duriug  the 
epidemic  season  might  carry  the  specific  germ  in  their  intestine,  and 
that  upon  their  death  from  another  disease  it  might  invade  the  tissues. 
I  was  therefore  not  willing  to  exclude  this  bacillus  until  I  had  found  it 
in  comparative  autopsies  made  outside  of  the  area  of  possible  yellow- 
fever  infection.  Having  found  it  in  my  comparative  autopsy  IS'o.  15, 
made  in  the  city  of  Baltimore,  in  January,  1890,  I  can  no  longer  enter- 
tain the  supposition  that  it  may  be  concerned  in  the  etiology  of  yellow 
fever. 

(e)   RESULTS   OF  EXPERIMENTS  UPON  ANIMALS. 

I  shall  give  an  account  of  my  experiments  with  pure  cultures  of  the 
various  bacteria  which  I  have  isolated  in  connection  with  my  systematic 
description  of  these  microorganisms.  At  present  it  is  ray  intention  to 
record  the  results  obtained  from  inoculations  of  blood,  urine,  liver 
tissue,  and  material  from  the  stomach  and  intestine,  and  first  it  will  be 
well  to  call  attention  to  similar  experiments  which  have  been  made  by 
others.  I  quote  from  my  previous  report,  published  in  the  annual 
volume  of  the  Marine- Hospital  Service  for  1889. 


124  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


We  qnote  as  follows  from  Dr.  Freire's  principal  work  (Doctrine  Microbienne  de  la 
Fievre,  Janne,  1855)  : 

"My  first  experiments  made  upon  the  monkey  and  the  dog  gave  a  negative  result 

(p.  35). 

"I  have  also  inoculated  black  vomit  into  a  dog,  repeating  the  injection  twice,  at 
intervals  of  some  days.  *  *  *  No  phenomenon  indicative  of  yellow  fever  mani- 
fested itself  (p.  36). 

"Fowls  and  pigeons  also  enjoy  a  complete  immunity,  as  we  shall  see  further  on. 
After  having  inoculated  tbese  animals  with  blood  drawn  directly  from  the  corpses  of 
yellow-fever  patients,  and  also  with  cultures  of  different  degrees  of  transplantation, 
without  having  succeeded  in  any  case  in  transmitting  to  them  the  malady,  I  turned 
my  attention  to  other  animals,  to  rabbits  and  to  gninea-pigs. 

"My  attention  was  especially  called  to  guinea-pigs  because  a  merchant  of  the 
place  said  to  me  that  just  when  the  epidemic  had  attained  its  maxium  of  intensity  he 
supported  an  enormous  loss  on  account  of  the  iK-ste.  which  killed  each  day  a  great 
number  of  his  guinea-pigs  "  (p.  36). 

We  remark  that  the  guinea-pig  is  very  subject  to  various  forms  or 
septicaemia,  and  that  tliose  wlio  have  endeavored  to  raise  them  in  lati- 
tudes ^here  yellow  fever  does  not  prevail  have  often  experienced  heavy 
losses,  especially  during  hot  weather  and  when  their  cages  are  not  care- 
fully cleaned.  My  guinea-pigs  in  Havana  in  1879  did  not  contract 
yellow  fever,  although  they  were  exposed  on  an  infected  ship  during 
the  hottest  part  of  the  year  for  a  period  of  48  hours.  Moreover,  Dr. 
Freire  himself  gives  evidence  that  during  the  winter  months  he  inocu- 
lated these  little  animals  with  blood  from  yellow  fever  patients  without 
result.    He  says : 

"  The  influence  of  season  upon  the  evolution  of  the  microbe  of  yellow  fever  is  very 
powerful.  For  the  purpose  of  determining  the  nature  of  this  influence  we  have  pro- 
ceeded to  various  experimental  researches.  We  have  inoculated  a  large  number  of 
guinea-pigs,  not  only  by  the  method  of  vaccination  but  also  by  subcutaneous  injec- 
tion of  cultures  of  the  microbe  in  gelatine.  These  cultures  showed  themselves  fertile 
in  characteristic  organisms,  and  their  energy  had  already  been  proved,  since  their  in- 
oculations had  caused  the  death  of  several  animals.  Very  well ;  these  inoculations 
made  in  July  and  August  have  given  only  negative  results.  The  animals  presented 
a  slicht  elevation  of  temperature,  but  survived  the  consequences  of  the  inoculation. 
Even  the  blood  of  patients  sick  with  yellow  fever  inoculated  into  animals  iu  the 
months  of  July  and  August  could  not  cause  their  death.  Indeed,  on  the  15th  of  August 
we  have  injected  with  the  blood  of  a  patient  attacked  with  yellow  fever  nine  guinea 
pigs.     The  following  is  the  course  of  the  temperature  as  observed: 


Before 
tlie  exper- 
iment. 

After  injection. 

'Sum'bcT. 

July  16. 

July  17. 

Jnly  18. 

Jnly  19. 

J                                                      

o 

38.9 

38.8 

39.0 

38.6 

39.0 

38.8 

39.1 

39.2 

38.8 

o 
39.0 

38.7 
39.0 
39.9 
39.2 
39.0 
39.0 
39.2 
38.2 

0 

37.8 
39.0 
38.0 
38.9 
38.0 
38.8 
38.5 
37.4 
39.6 

o 

38.2 

39.0 

38.4 

38.8 

39.9 

39.8 

38.9 

39.0 

39.2 

o 
39.0 

2                                   

39.6 

3 

38.8 

i 

38.6 

39.0 

6                                            

40.0 

7    

30.4 

8                    

38.5 

9 

38.5 

ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  125 

"The  following  days  tbe  temperatures  of  nearly  all  of  these  animals  hecamo  uor« 
iiial.  None  of  them  died.  The  fact  shows  the  innocuity,  due  to  a  change  of  season, 
of  the  inoculations  which  a  month  previously  showed  themselves  virulent  and  so 
toxic  that  they  infallihly  caused  the  death  of  all  the  animals"  (p.  235). 

Dr.  Freire  has  referred  to  tbe  experiments  of  Dr.  Range,  "Medecin 
de  [)reniiere  classe,"  of  the  French  nav^^,  as  confirming  his  own.  These 
experiments  were  made  during  an  epidemic,  which  occurred  in  1885, 
upon  the  lies  du  Saint  (Gruayana). 

The  inoculation  experiments  of  Dr.  Eange  were  made  during  the 
height  of  the  epidemic^  iu  the  month  of  April.     He  says: 

"In  guinea-pigs  inoculation  of  hlood  taken  directly  from  the  patient  was  not  fol- 
lowed by  any  result.  Inoculations  with  Mack  vomit,  cultures  from  hlood,  or  cultures 
from  black  vomit  gave  always  a  positive  result;  that  is  to  say,  they  were  followed  by 
reactioual  phenomena.     Four  times  they  determined  death." 

These  cultures,  like  those  of  Dr.  Freire  and  others  obtained  from  the 
same  source,  no  doubt  contained  various  organisms,  and  among  them  one 
or  more  may  have  been  pathogenic  for  the  guinea-i)ig ;  but  the  experi- 
ments made  have  shown  most  definitely  that  blood  drawn  directly  from 
the  patient  during  the  epidemic  season  does  not  kill  guinea-pigs.  We 
must  therefore  conclude  that  the  death  of  guinea  pigs  inoculated  by  Dr. 
Freire  during  the  epidemic  season  resulted  not  from  yellow  fever,  but 
from  inoculation  with  some  pathogenic  organism  which  was  abundant 
during  the  summer  months,  and  consequently  was  present  iu  his  cul- 
tures, or  from  accidental  inoculation  through  the  wound  made  by  him 
in  his  experiments.  The  guinea-pig  is  very  subject  to  the  last-men- 
tioned accident,  especially  when  kept  iu  foul  cages.  Its  own  discharges 
and  the  remnants  of  food  in  its  cage  furnish  a  pabulum  in  which  a  mul- 
titude of  microorganisms  are  to  be  found.  Owing  to  the  shortness  of 
its  legs  its  abdomen  is  constantly  soiled  with  this  material,  and  if  any 
pathogenic  organism  is  present  an  inoculation  wound  made  for  experi- 
mental pur[)0ses  can  scarcely  fail  to  be  infected  with  it. 

It  is  scarcely  worth  while  to  give  in  detail  the  experiments  upon 
guinea-pigs  made  by  Freire  in  which  death  followed  the  inoculation, 
and  in  every  one  of  which  the  assumption  is  made  that  the  animals 
succumbed  to  yellow  fever.  But  his  summary  statement  of  these  exper- 
iments presents  some  points  of  interest.  Thus  we  find  that  one  ani- 
mal died  at  the  end  of  a  few  hours,  while  one  lived  for  30  days.  Yet 
death  in  both  of  these  extreme  cases  is  ascribed  to  yellow  fever,  resulting 
from  the  inoculation  practiced. 

BLOOD    AND    LIVEE    TISSUE    FROM  A  RECENT    AUTOPSY  NOT  PATHO- 
GENIC  FOR   GUINEA-PIGS   OR   RABBITS. 

My  experiments  made  in  Havana  during  the  epidemic  season  fully  con- 
firm those  of  Eange  as  to  the  innocuity  of  yellow  fever  blood  when  in- 
jected into  guinea-pigs  in  considerable  quantity.  This  is  shown  by  the 
following  experiments : 


126  ETIOLOGY    AND    PREVENTION    OP    YELLOW    FEVER. 

May  13, 1389.— lujectcdoue-fourtliof  acubic  ccutimetre  of  blood  obtained  at  autopsy 
from  heart  of  case  7  iuto  the  abdominal  cavity  of  a  very  small  guiuca-pig.  Result 
negative. 

May  13,  1889.— Injected  one-half  of  a  cubic  centimetre  of  blood  serum  from  heart  of 
case  17  into  cavity  of  the  abdomen  of  another  small  guinea-pig.     Result  negative. 

May  23,  18S9.— Injected  subcutaneously  and  also  in  cavity  of  abdomen  a  small 
amount  of  crushed  liver  tissue  from  case  19  into  guinea-pig  No.  54.     No  result. 

May  26,  1889.— Injected  into  snbcutaneous  tissue  of  guinea-pig  No.  58  one-half 
of  a  cubic  centimetre  crushed  liver  tissue  from  case  20.     No  result. 

J/me  4,  1889.— Injected  subcutaneously  into  guinea-pig  No.  82  5  minims  of  crushed 
liver  tissue  from  case  22.     No  result. 

June  13,  1889.— Injected  subcutaneously  into  guinea-pig  No.  100  one-half  of  a  cubic 
centimetre  blood  and  crushed  parenchyma  from  liver  of  case  24.     No  result. 

June  13,  1869.— Injected  subcutaneously  into  guinea-pig  No.  101  one  cubic  centi- 
metre blood  and  crushed  tissue  from  kidney,  case  24.     No  result. 

June  29,  1889.— Injected  subcutaneously  into  guinea-pig  No.  126  one  half  of  a  cubic 
centimetre  blood  and  liver  pulp  from  case  25.     No  result. 

All  of  these  injections  were  made  with  material  in  which  no  micro- 
organisms were  recognized  in  smear  preparation  stained  with  fnchsin. 
In  the  foUowiiig  cases  in  which  death  followed  the  inoculation  micro- 
organisms were  present: 

May  27,  1889.— Injected  subcutaneously  into  guinea-pig  60  (quite  small)  4  minims 
of  material  from  liver  of  case  21,  just  collected.  This  animal  was  found  dead  at  6  a.  m., 
on  the  morning  of  May  28.  The  autopsy  showed  extensive  subcutaneous  ojderaa 
extending  from  point  of  inoculation,  and  the  effused  serum  contained  a  large  anaerobic 
bacillus,  my  bacillus  N. 

July  16,  7.30  a.  m.— Injected  subcutaneously  into  guinea-pig  No.  153,  5  minims  of 
blood  from  liver,  case  28,  containing  a  large  bacillus;  slide  1325  (N  ?).  The  animal 
died  at  10  p.  m.  Extensive  subcutaneous  effusion  of  bloody  serum.  Bacillus  N  re- 
covered from  liver. 

These  experiments  show  tliat  blood  and  liver  tissue  obtained  at  recent 
autopsies  do  not,  as  a  rule,  kill  guinea-pigs,  but  that  iu  exceptional 
cases,  in  which  the  large  anaerobic  bacillus  is  present,  which  I  have 
designated  by  the  letter  N,  death  may  occur  very  promptly. 

I  have  also  obtained  negative  results  from  injections  of  fresh  liver 
tissue  into  rabbits. 

August  9,  1889.— Injected  subcutaneously  into  rabbit  No.  158  2  minims  of  crushed 
liver  tissue  from  case  30.     Result  negative. 

August  12,  1889.— Injected  subcutaneously  into  rabbit  164  5  minims  of  material 
from  liver  of  case  32.     Result  negative. 

August  13,  1889.— Injected  subcutaneously  into  rabbit  189  4  minims  of  material 
from  liver  of  case  33.     Contains  bacillus  N,  slide  142G.     Result  negative. 

August  15,  1889.— Injected  subcutaneously  1  cubic  centimetre  material  from  liver  of 
case  35,  principally  blood,  into  rabbit  170.     Result  negative. 

August  19,  1883. — Injected  subcutaneously  one-half  of  a  cubic  centimetre  material 
from  liver  of  case  36  iuto  rabbit  178.     Result  negative. 

August 21,  1889.— Injected  subcutaneously  into  rabbit  183  2  minims  material  from 
liver  of  case  37.     Result  negative. 

Axigust  22,  1889. — Injected  subcutaneously  1  cubic  centimetre  blood  and  liver  tissue 
from  case  38  into  rabbit  184.     Result  negative. 

These  experiments  suffice  to  show  that  as  a  rule  blood  and  liver  tis- 
sue from  a  recent  autopsy  is  not  pathogenic  for  rabbits.    But  in  the 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  127 

following  case  death  resulted  from  the  subcutaueous  iujectiou  of  similar 
material : 

August  10,  1&89. — Injected  snljcntancously  into  rabbit  159  3  minims  from  liver  of 
case  31.     Animal  died  iu  couvnlsions  at  1  p.  m.,  August  12. 

The  bacillus  of  rabbit  septictemia  was  recovered  from  the  liver  in  an 
agar-stick  culture. 

The  same  bacillus  was  obtained  indirectly  from  another  case,  as 
follows : 

Guinea-pig  No.  172  injected  July  31  with  material  from  liver  of  case 
29,  kept  48  hours  in  an  antiseptic  wrapping,  died  the  following  day. 
Anaerobic  culture  iu  glycerin  agar  from  the  liver  of  this  guinea-pig 
contained  bacilli  and  was  injected  (1  cubic  centimetre)  into  guinea-jng 
141,  which  died  at  the  end  of  32  hours  from  the  time  of  injection.  An 
anaerobic  culture  in  blood  serum  from  the  liver  of  this  guinea-pig  was 
injected  on  August  G  into  rabbit  150,  which  died  the  following  day. 
The  blood  and  liver  of  this  rabbit  contained  a  small  bacillus  with 
stained  ends,  which  proved  to  be  the  bacillus  of  rabbit  septicaemia. 
Cultures  from  the  blood  and  liver  of  this  rabbit  and  the  preceding  one 
were  subsequently  injected  into  other  rabbits  with  a  uniformly  fatal 
result,  and  the  bacillus  was  fully  identified  as  Koch's  bacillus  of  rab- 
bit septicaemia,  now  generally  admitted  to  be  identical  with  the  bacillus 
of  fowl  cholera,  first  described  by  Pasteur  as  a  micrococcus. 

YELLOW  FEVER   URINE   NOT   TATHOGENIC   FOR   RABBITS. 

May  5,  1889. — Injected  into  cavity  of  abdomen  of  ralibit  101  7  cubic  centimetres 
urine  from  case  16,  drawn  at  autopsy  through  walls  of  bladder.     Result  negative. 

May  10,  1889. — Injected  into  cavity  of  abdomen  of  rabbit  105  (weight  1,000  grammes) 
11  cubic  centimetres  of  albuminous  yellow  fever  urine  from  a  case  in  the  third  day  of 
the  disease.  Temperature,  30  minutes  after  the  injection,  104°  F.  ;  respiration  nor- 
mal.    The  animal  remained  in  good  health  until  used  for  anotlier  experiment. 

July  29,  1889. — Injected  into  cavity  of  abdomen  of  rabbit  133  (weight  about  1,000 
grammes)  10  cubic  centimetres  of  highly  albuminous  urine  from  a  case  in  the  fourth 
day  of  the  disease;  urine  collected  two  hours  before  injection;  slightly  acid;  specific 
gravity,  1.025.     Result  negative. 

VIRULENCE   OF  LIVER   TISSUE   KEPT   FOR   18  HOURS   IN  AN  ANTISEP- 
TIC WRAPPING. 

I  have  already  referred  to  the  fact  that  a  piece  of  liver  or  kidney 
from  a  yellow-fever  patient  which  has  been  enveloped  in  an  antiseptic 
wrapping  at  the  time  of  the  autopsy  contains  numerous  microorgan- 
isms when  the  antiseptic  wrapping  is  removed  at  the  end  of  48  liours. 
Now,  if  a  little  material  from  the  interior  of  one  of  these  pieces  is  in- 
jected beneath  the  skin  of  a  guinea-pig  my  experiments  show  that 
death  generally  occurs  within  a  comparatively  short  time.  Very  shortly 
after  the  injection  is  made  the  animal  becomes  restless,  and  at  the  end 
of  3  or  4  hours  he  commences  to  dash  about  his  cage  at  intervals  in  an 
abrupt,  "  nervous"  way.    Death  frequently  occurs  inside  of  24  hours, 


128     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER 

and  at  the  autopsy  an  extensive  accumulation  of  bloody  serum  is  found 
in  the  subcutaneous  connective  tissue.  This  gravitates  to  the  most  de- 
pendent position,  and  commonly  the  entire  wall  of  the  abdomen  is  filled 
with  the  bloody  fluid,  which  accumulates  to  such  an  extent  as  to  form 
a  large  fluctuating  pouch. 

The  effused  bloody  serum  usually  contains  various  bacilli,  among 
which  the  most  conspicuous  is  my  bacillus  K,  which  is  sometimes  ijresent 
in  great  numbers  and  almost  in  a  pure  culture.  This  bacillus  does  not 
invade  the  blood  and  is  not  found  in  smear  preparations  or  cultures 
from  blood  taken  from  the  heart  or  material  from  the  liver.  Cultures 
from  the  liver  or  blood,  however,  almost  always  give  one  or  more  bacilli, 
which  have  been  associated  with  bacillus  N  in  the  liver  tissue,  pre- 
served for  48  hours,  and  which  was  used  for  the  inoculation.  Very 
commonly  I  have  obtained  in  these  cultures  my  bacillus  a  or  bacillus  x, 
or  both  of  these. 

Two  or  three  minims  of  the  bloody  serum  present  in  the  subcutaneous 
tissue  injected  into  another  guinea-pig  also  causes  death  with  the  same 
symptoms  and  pathological  appearances,  and  in  the  same  way  a  third 
may  be  inoculated  from  the  second,  and  so  on.  But  the  virulence 
appears  to  diminish,  the  time  before  death  being  prolonged  in  the  case 
of  the  second  and  third  animals  in  a  series,  and  beyond  this  a  fatal 
result  is  not  always  produced. 

NOTES  OF  EXPERIMENTS  MADE  IN  HAVANA  IN  1889. 

Mai/li,  ip.m. — Injected  subcutaueonsly  into  guinea-pig  No.  43  a  small  amount 
of  crushed  liver  parenchyma  from  piece  kept  48  hours  in  antiseptic  wrapping,  from 
case  18.  The  animal  was  found  dead  at  6  o'clock  a.  m.,  May  16.  There  was  an  ex- 
tensive collection  of  bloody  serum  in  the  subcutaneous  connective  tissue,  which  con- 
tained bacillus  N  in  large  numbers  and  other  bacilli.  The  liver  was  dark  in  color 
and  rather  soft,  spleen  normal. 

May  16,  10  a.  m. — Injected  subcutaneously  3  minims  of  bloody  sernm  from  subcu- 
taneous connective  tissue  of  guinea-pig  No.  43,  into  guinea-pig  No.  45.  Died  morning 
of  May  21,  extensive  subcutaneous  oedema;  liver  and  spleen  normal  and  do  not  con- 
tain bacilli. 

Ma ij  24,  4  p.  m. — Injected  subcutaneously  into  guinea-pig  No.  56,  2  minims  from 
liver  of  case  19,  kept  48  hours  in  laboratory.  Found  dead  at  6  a.  m.,  May  29.  No 
subcutaneous  oedema;  gall  bladder  much  distended;  no  microorganisms  in  liver; 
abdominal  viscera  normal  in  appearance.  Pure  culture  of  bacillus  ic  obtained  from 
blood  of  heart. 

July  5,  1  p.  TO. — Injected  subcutaneously  into  guinea-pig  100,  2  minims  of  material 
from  liver  of  case  27,  48  hours  in  antiseptic  wrapping.  July  6,  4  p.  m.  the  animal 
dying  and  was  killed.  Slight  subcutaneous  ojdema.  Abdominal  viscera  normal  in 
appearance.     Pure  culture  of  bacillus  x  obtained  from  blood  of  heart. 

July  31,  9:30  a.  to. — Injected  subcutaneously  into  guinea-pig  No.  172.  2  minims  of 
material  from  liver,  case  29,  48  hours  in  antiseptic  wrapping.  Died  at  11:30  a.  m. 
the  next  day.  No  subcutaneous  oedema ;  spleen  very  large  and  dark  in  color ;  small 
intestine  hypera^mic  and  contains  a  bloody  fluid.  No  microorganisms  in  culture  from 
liver  and  blood  from  heart  in  aqua  coco.  Anaerobic  culture  in  aqua  coco  contains  a 
bacillus  having  vibrio-like  movements. 

August  11,  10  a.  to. — Injected  subcutaneously  into  guinea-pig  185,  3  minims  from 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  129 

liver  of  case  30,  48  hours  iu  antiseptic  wrapping.  Dead  August  13,  at  6  a.  m.  Exten- 
sive subcutaneous  oedema.  Cultures  iu  aerobic  gelatine  tubes  from  subcutaneous 
bloody  serum  contain  colon  bacillus. 

August  15,  2:30  p.  m. — Injected  subcutaueously  into  guinea-pig  No.  190,  4  minims 
of  material  from  liver  of  case  21,  48  hours  in  antiseptic  wrapping;  contains  bacillus 
N.     Animal  found  dead  at  6  a.  m.  the  next  morning. 

August  21,  11:30  a.  m. — Injected  subcutaueously  1  minim  from  liver  of  case  36,  pre- 
served for  48  hours  iu  antiseptic  vrrappiug.     No  result. 

August  24,  12  m. — Injected  subcutaueously  into  guinea-pig  187,  2  minims  of  mate- 
rial from  liver  of  case  38,  preserved  48  hours  in  an  antiseptic  wrapping.  Found  dead 
at  6  a.  m.  the  next  morning.  Usual  subcutaneous  cedema  containing  bacillus  N 
slide  1470. 

EXPERIMENTS  UPOX   RABBITS. 

August  11,  1889.— Injected  subcutaneously  into  rabbit,  No.  161,  4  minims  of  material 
from  liver  of  case  17,  kept  36  hours  iu  antiseptic  wrapping;  coutaius  bacillus  N. 
Result  negative. 

Note  : — Three  minims  of  the  same  material  killed  guiuea-i)ig  No.  185. 

August  17,  1889. — Injected  subcutaueously  4  minims  of  material  from  liver  of  case 
35,  kept  for  48  hours  in  au  antiseptic  wrapping,  into  rabbit  No.  176.  No  subcutane- 
ous oedema.     A  motile  bacillus  recovered  iu  aerobic  culture  from  liver;  slide  1461. 

July  30,  3:30^.  m. — Injected  subcutaneously  into  rabbit  136,  10,  minims  of  bloody 
serum  from  subcutaneous  connective  tissues  of  guinea-pig  134;  contains  bacillus  N 
and  other  bacilli ;  slide  1369.  Animal  found  dead  at  5  a.  m.  the  next  day.  Some  sub- 
cutaneous oedema. 

July  31,  9  a.  m. — Injected  subcutaneously  into  rabbit  139,  2  minims  of  bloody  serum 
from  cellular  tissue  of  rabbit  136.  Animal  died  at  9  p.  m.  the  same  day.  Very  littlo 
subcutaneous  cedema. 

August  11,  10  a.  m. — Injected  subcutaneously  into  rabbit  No.  161,  4  minims  of 
material  from  liver  of  case  17,  preserved  36  hours  in  an  antiseptic  wrapping;  contains 
bacillus  N.     Result  negative. 

August  11,  3  jj.  m. — lujected  subcutaneously  into  rabbit  162,  5  minims  bloody  serum 
from  cellular  tissue  of  guinea-pig  150,  just  dead,  containing  bacillus  N  and  other 
bacilli ;  slide  1415.  The  auimal  died  at  10:30,  August  15  ;  abscess  in  middle  of  belly, 
liver  dark  iu  color,  spleen  normal.  The  liver  of  this  rabbit,  kept  48  hours  in  antisep- 
tic wrapping  ;  had  on  acid  reaction  and  contained  bacillus  N. 

August  17,  9:30  a.  m. — lujected  subcutaueously  into  rabbit  No.  176.  4  minims  of 
material  from  liver  of  case  22,  48  hours  in  antiseptic  wrapping;  contains  bacillus  N  ; 
slide  1442.  Dead  August  21  at  6  a.  m.  A  motile  aerobic  bacillus  obtained  iu  culture 
from  liver ;  slide  1461.     No  subcutaneous  cedema. 

COMPARATIVE  EXPERIMENTS. 

June  1,  1889, 10  a,  m. — Injected  subcutaneously  into  guinea-pig  No.  72,  3  minims 
of  material  from  liver  of  case  ot  tuberculosis,  kept  48  hours  in  antiseptic  wrapi)ing ; 
slide  1187  (comparative  autopsy  No.  6).  Animal  found  dead  the  next  day  at  6  a.  m. 
Extensive  collection  of  bloody  serum  containing  bacilli  in  subcutaneous  tissues; 
slide  1193. 

November  20,  1889,  Z  p.  m. — lujected  subcutaneously  into  guinea-pig  No.  173,  a  little 
material  from  interior  of  piece  of  liver  kept  in  antiseptic  wrapping  for  48  hours,  from 
comparative  autopsy  No.  10  ;  slide  1517.  Animal  found  dead  at  9  a.  ra.  the  next  day. 
Extensive  subcutaneous  cedema;  containing  various  bacilli ;  slide  1581.  Spleen  en- 
larged; no  microorganisms  recognized  in  smear  preparation. 

Noveniber  22,  10:30  a.  m. — lujected  sub-cutaneously  2  minims  bloody  serum  from, 
connective  tissue  of  guinea-pig  No.  173  (above)  into  guinea-pig  No.  174.  Animal  died 
4067- 9 


130  ETIOLOGl'    AND    PEEVENTION    OF    YELLOW    FEVER. 

at  3:30  p.  m.,  November  23.  Considerable  subcutaueous  oedema  (slide  1526),  from 
Avbicli  cultures  iugelatiue  roll  tubes  give  a  liquefyiug  bacillus  of  the  proteus  group. 

November  30. — A  culture  of  this  liquefyiug  bacillus  iu  agua  coco,  injected  subcutane- 
ously  into  guinea  pig  No.  176,  gave  a  negative  result. 

November  2'.^,  4jj.  m. — Injected  subcutancously  3  minims  bloody  serum  from  cellu- 
lar tissues  of  guinea-pig  No.  174.  Animal  found  dead  on  the  moruingof  November  25. 
Extensive  subcutaneous  tudema  containing  bacilli  (slide  1527).  Liquefying  bacillus 
recovered  from  liver. 

November  25. — Injected  subcutaneously  2  minims  bloody  serum  from  guinea-pig 
No.  177.     Animal  recovered. 

November  30,  ^  p.  m.,  1889. — Injected  subcutaneously  2  minims  material  from  liver 
of  comparative  autopsy  No.  13,  preserved  48  hours  iu  antiseptic  vrrapping,  into  guinea 
pig  No.  181.  Dead  next  morning  at  9  o'clock.  Extensive  subcutaueous  eifusion  of 
bloody  serum  -with  separation  of  integument;  bloody  serum  contains  a  loug  bacillus 
(slide  1544). 

December  2.  3:30  j).  7)i. — Injected  subcutaneously  3  minims  bloodj- serum  from  cellu- 
lar tissue  of  guinea-pig  No.  181,  into  guinea-pig  No.  182  (uuxterial  had  been  kept  24 
hours  in  laboratory  in  the  sterilized  collecting  bulb).  Annual  found  dead  at  9  a.  m., 
December  5.  Extensive  subcutaneous  collection  of  bloody  serum  which  contains  A^ari- 
ous  bacilli  (slide  1556).   Gelatine  roll-tubes  contain  a  liquefying  bacillus,  a  proteus. 

December  5,  11  a.  m. — Injected  subcutaueously  3  minims  of  bloody  serum  from  cel- 
lular tissue  of  guinea-pig  182,  into  guinea-iiig  No.  185.  Found  dead  next  morning. 
Some  subcutaneous  ojdema  (slide  1559). 

December  6,  9  a.  m. — Injected  subcutaneously  into  guinea-pig  186,  3  minims  of  bloody 
serum  from  cellular  tissue  of  guiuea-pig  185.     Animal  recovered. 

January  4,  3jj.  m.,  1890. — Injected  subcutaneously  3  minims  of  material  from  liver, 
comparative  autopsy  No.  14,  kept  48  hours  in  antiseptic  wrapping,  into  guiuea-pig 
191;  contains  a  large  bacillus  resembling  N;  slide  1.592.  Animal  died  next  day  at  3 
p.  m.  Extensive  collection  of  bloody  serum  iu  subcutaneous  connective  tissue  con- 
taining bacillus  N ;  colon  bacillus  obtained  in  culture  from  liver. 

January  5,  5  2>-  m. — Injected  subcutaneously  into  guinea-pig  193,  4  minims  of  bloody 
serumTrom  cellular  tissue  of  guinea-pig  191.  Animal  very  feeble  and  killed  at  5  p.  m., 
January  6.     Extensive  subcutaneous  cedema  ;   bloody  serum  contains  bacillus  N. 

January  6,5  jj.  m. — Injected  subcutaueouslj'  into  guinea-pig  194,  4  minims  of  bloody 
serum  from  cellular  tissue  of  guinea-pig  193.  Found  dead  at  9  a.  m.,  Januarj'^  8.  No 
subcutaneous  cedema;  liver  dark  in  color  and  full  of  blood  ;  sideen  enlarged;  colon 
bacillus  recovered  from  liver. 

These  comparative  experiments  suffice  to  show  that  the  virulence  of 
liver  tissue  Icept  for  18  hours  in  an  antisejjtio  ivrappimj  is  not  peGuUar  to 
yelloiv  fever. 

BLATERIAL   OBTAINED   FROM    THE    STOMACH    SOON   AFTER    DEATH    IS 
VIRULENT   FOR   GUINEA   I'lGS. 

The  stomach  is  usually  found  to  contain  a  considerable  quantity  of 
fluid,  which  may  correspond  with  that  ejected  durin-^-  the  last  hours  of 
life — "black  vomit" — or  may  be  a  grumous  and  thick  fluid,  having  a 
brownish  color,  and  containing  a  variety  of  microorganisms,  together 
with  the  desquamated  epithelium  of  the  stomach. 

Aerobic  cultures  from  this  material  show  the  presence  of  a  variety  of 
microorganisms,  among  which  the  most  constant  and  most  abundant  is 
iny  bacillus  a.    Yarious  anaerobic  bacilli  are  also  present,  including  my 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  131 

bacillus  iST.     This  material  injected  into  guinea-pigs  usually  produces 
a  fatal  result  within  24  hours. 

June  4,  10  a.  m. — Injected  «ubcataueously  into  gniuea-pig,  No.  SO,  3  minims  of  fluid 
obtained  at  autop.sy  from  stomacli  of  case  25.  At  1:30  tlie  auiiuai  was  observed  to 
be  very  restless.  Found  dead  the  next  day  at  6  a.  m.  Extensive  subcutaneous 
u-dema,  and  softeuing  of  abdomiual  muscles. 

June  4,  10  a.  m. — Injected  subcutaueously  into  guinea-iiig  84,  one-lialf  of  a  cubic 
centimetre  black  vomit  from  stomacli  of  case  23,  obtained  at  autojjsy.  Died  at  4  p. 
m.  next  day.     Extensive  subcutaneous  cedema. 

June  29,  1  p.  /n.— Injected  subcutaueously  into  guinea-pig  124,  2  minims  of  dark 
grumous  material  from  stomach  ;  case  25,  acid  reaction.     No  result. 

July  3,  12:30. — Injected  subcutaueously  into  guinea-pig  128,  3  minims  of  bloody  fluid 
from  stomach,  case  27.  Died  at  1:30  July  4.  Extensive  subcutaneoiisa'dema.  Culture 
from  liver  several  difterent  bacilli  (slide  1281),     Culture  from  heart,  colon  bacillus. 

July  1(5,  7  a.  ?h. ^Injected  subcutaueously  into  guinea-pig  152,  5  minims  of  bloody 
fluid  from  stomach  of  case  28.  Auimaldiedat  12  m.,  July  17.  Extensive  subcutaneous 
ojdema. 

TY^PICAL   "BLACK  V03IIT "   COLLECTED   DURING  LIFE   AND   INJECTED 
AT   ONCE   INTO    OUINEA-PIGS   IS   NOT  PATHOGENIC. 

June  27,  10  a.  m. — Injected  subcutaneously  into  guinea-pig  No.  122,  1  cubic  centi- 
metre black  vomit  from  yellow  fever  case  in  military  hospital  (typical  black  vomit 
•with  very  acid  reaction).     Result  negative. 

July  S,  4j>.  m. — Injected  subcutaueously  into  guinea-pig  139,  1  cubic  centimetre  of 
acid  black  vomit  from  case  in  military  hospital,  sick  7  days.     Result  negative. 

July  8,  4  p.  m'. — Injected  subcutaueously  into  guinea-pig  140,  oue-half  of  a  cubic 
centimetre,  acid  hlaek  vomit  (same  as  iu  guiuea-pig  139).     Result  negative. 

1  may  remark  here  that  my  culture  experiments  with  black  vomit 
have  several  times  given  an  entirely  negative  result.  (Aerobic  cultures 
in  Hesh-peptone-gelatiue). 

MATERIAL  OBTAINED  FROM  THE  S3IALL  INTESTINE  OF  YELLOW 
FEVER  PATIENTS  AT  AUTOPSIES  MADE  SOON  AFTER  DEATH  IS 
VERY  VIRULENT  WHEN  IN.JECTED  BENEATH  THE  SKIN  OF  GUINEA- 
PIGS. 

The  contents  of  the  small  intestine  in  yellow  fever  cases  in  which 
death  has  occurred  at  the  end  of  4  to  8  days  are  usually  dark  in  color 
and  quite  viscid  from  the  ijresence  of  mucus.  The  small  intestine  is 
lined  with  this  viscid  black  matter,  which  shows  through  its  walls  and 
gives  it  the  api^earance  of  being  full  of  a  dark  substance  ;  but  ui^on 
cutting  itopen  the  quantity  is  commonly  found  to  be  small ;  sometimes, 
however,  the  intestine  is  filled  with  a  thin  black  fluid  resembling  black 
vomit.  A^o  doubt  the  dark  color  of  the  material  contained  in  the  intes- 
tine, like  that  of  black  vomit,  is  due  to  the  presence  of  blood  ijigment 
changed  by  the  acid  secretions,  and  I  am  inclined  to  think  that  as  a 
rule  this  pigment  comes  from  the  stomach  and  is  not  due  to  intes- 
tinal hemorrhage.  Although  considerable  quantities  of  black  vomit 
are  often  ejected  by  the  mouth,  there  can  be  little  doubt  that  a  portion 
of  this  fluid  passes  into  the  intestine,  and  that  the  liquid  portion  is  reab- 


132     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVEK. 

sorbed  leaving  the  precipitated  blood  pigment,  mixed  with  intestinal 
mncus,  as  a  tbin  viscid  layer  upon  the  surface  of  the  mucous  membrane. 
This  is  the  material  which  I  have  collected  at  my  autopsies,  and  which 
has  served  for  my  culture  and  inoculation  experiments. 

Smear  preparations  stained  with  fuchsin  show  that  this  material  con- 
tains very  numerous  and  various  bacilli. 

May  26,  9:30  a.  m.— Injected  subcutaneously  into  guiuea-pig  59,  2  minims  material 
from  intestine,  case  20.  Animal  died  at  1:30  p.  m..  May  27.  Extensive  collection  of 
bloody  serum  iu  subcutaneons  connective  tissue.  A  few  bacilli  in  liver  on  direct 
examination.  Spleen  rather  large  ;  liver  normal.  A  liquefying  bacillus  obtained  in 
cultures  from  liver. 

May  28,  12  hi.— Two  drops  of  bloody  serum  from  cellular  tissue  of  above  guinea-pig, 
No.  59,  injected  beneath  the  skin  of  guiuea-pig  No.  62.  The  animal  died  at  G:30  p. 
m.,  the  same  day.  Extensive  effusion  of  bloody  serum  and  separation  of  the  skin 
from  subcutaneous  tissues  over  entire  abdomen.  Various  bacilli  present  in  this 
bloody  serum,  including  one  which  liquefies  gelatine. 

May  29,  2:30  j>.  ?»i. — Two  minims  of  bloody  serum  from  cellular  tissue  of  above 
o-uinea-pig  No.  62,  injected  beneath  the  skin  of  guinea-pig  28.  Animal  died  at  4  p. 
m.,  May  31.  Extensive  subcutaneous  tedema  with  iuilainmatory  thickening  of  tissues. 
Cultures  from  cellular  tissue  and  liver  give  an  actively  motile  aerobic,  liquefying 
bacillus ;   slide  1198. 

June  1  10  a.  m. — One  minim  of  bloody  serum  from  cellular  tissue  of  above  guinea 
pig  No.  68,  injected  beneath  the  skin  of  guinea-pig  No.  71.  Found  dead  morning  of 
June  3.  But  little  subcutaneous  oedema ;  abdominal  viscera  normal ;  bacillus  coli 
commune  in  gelatine  stick  culture  from  blood  of  heart. 

May  27,  12  m.— Injected  subcutaneously  into  guinea-pig  61,  2  minims  material 
from  intestine,  case  21.  Found  dead  at  6  a.  m..  May  28,  Extensive  collection  of 
bloody  fluid  in  subcutaneous  connective  tissue. 

June  4, 10  a.  m. — Injected  subcutaneously  2  minims  material  from  intestine,  case  22, 
into  ouiuea-pig  81.  Died  at  4:30  p.  m.,  June  5.  Extensive  collection  of  bloody  serum 
in  subcutaneous  connective  tissue  containing  bacillus x. 

June  13,  12  m.— Injected  subcutaneously  3  minims  of  viscid  mucus,  not  black,  from 
intestine,  case  24,  into  guinea-pig  102,  Died  at  8:30,  June  14.  Bloody  serum  in  con- 
nective tissue  containing  bacillus  h;  this  serum  has  a  slightly  acid  reaction.  Abdom- 
inal organs  normal. 

June  14,  10  a.  m. — Three  minims  of  bloody  serum  from  cellular  tissue  of  abovb 
guinea-pig  No.  102,  injected  beneath  the  skin  of  guinea-pig  No.  105.  Died  at  7:30, 
June  15.  No  subcutaneous  oedema.  Abdominal  viscera  normal  in  appearance. 
A  few  bacilli  in  liver  and  blood  from  heart  on  direct  examination.  Bacillus  7i  recov- 
ered in  culture  from  blood  of  heart. 

July  2,  1:30  p.  ?ft.— Injected  subcutaneously  into  guinea-pig  127,  5  minims  of 
liquid  feces  from  case  of  yellow  fever  in  civil  hospital,  eighth  day  of  sickness. 
Animal  died  at  12  m.,  July  5.     Liver  rather  light  in  color  ;  spleen  enlarged. 

JitZj/ 3, 12:30  j>.  m. — Injected  subcutaneously  into  guinea-pig  129,  3  minims  bloody 
fluid  from  iutestine,  case  14  (slide  1276).  Died  at  2  p.  m.,  July  4.  Extensive 
subcutaneous  cedema.  Cultures  from  blood  of  heart  and  from  liver  contain  bacillus 
a,  also  a  micrococcus;  cultures  from  serum  in  connective  tissue,  bacillus  a  and 
a  liquefying  bacillus  (fc), 

July  4, 2:30_p.  m. — Injected  subcutaneously  into  guiuea-pig  133,2  minims  bloody 
serum  from  connective  tissue  of  guinea-pig  129.     Result  negative. 

July  3, 12:30  jj.  m.— Injected  subcutaneously  into  guinea-pig  130,4  minims  of  feces 
from  case  of  yellow  fever  on  German  brig  iu  harbor  ;  feces  yellow  in  color  liquid, 
alkaline  reaction.     Animal  found  dead  at  6  a.m,  next  morning.     Extensive  sub- 


ETIOLOGY   AND    PREVENTION    OF    YELLOW    FEVER.  133 

cutaneous  cedema  with  softeuiug  of  the  muscles.     Bacillus  g  recovered  from  effused 
serum  in  cellular  tissue  of  this  guinea-pig. 

July  6,  12:30  p.  m. — Injected  subcutaneously  1  cubic  centimetre  culture  from 
heart  of  guinea-pig  127  (see  above).  Died  July  7,  at  2:30  p.  m.  Same  subcuta- 
neous tedema  and  bloody  extravasation  ;  liver  rather  light  iu  color ;  uterus  intensely 
congested,  escape  of  bloody  fluid  from  vagina. 

July  16,7  a.m. — Injected  subcutaneously  into  guinea-pig  1.51,  2  minims  of  mate- 
rial from  intestine,  case  28,  black  viscid  mucus,  acid  reaction.  Animal  recovered  ; 
abscess  at  point  of  iuoculation  and  in  middle  of  belly. 

July  29,8  jy-'tn. — Injected  subcutaneously  into  guinea-pig  168,3  minims  material 
from  intestine,  case  29,  viscid  mucus,  not  black,  acid  (slide  1367).  Died  at  1  p.  m., 
July  30.  Extensive  collection  of  bloody  serum  iu  subcutaneous  tissues  and  soften- 
ing of  muscles  of  abdomen.     Bacillus  N  present. 

July  30,  3:15  p.  m. — Injected  subcutaneously  into  guinea-i)ig  169,  3  minims  of  bloody 
serum  from  cellular  tissue  of  guinea-pig  168.  Died  at  5  p.m.,  July  31.  Extensive 
subcutaneous  effusion  of  bloody  serum,  separation  of  skin  from  abdominal  walls, 
and  softening  of  abdominal  muscles.  Spleen  normal,  liver  rather  light  in  color 
contains  a  few  bacilli.     Various  bacilli  in  serum  from  cellular  tissue  (slide  1372). 

July 'SO,  3:30  j).  m. — Injected  subcutaneously  into  rabbit  136,  10  minims  bloody 
serum  from  guiuea-pig  168  (bacillus  N,  etc.).     Animal  found  dead  at  5  a.  m.,  July  31. 

July  31,  "J  a.  ?H.— Injected  subcutaneously  into  guiuea-pig  171,  3  minims  bloody 
serum  from  cellular  tissue  of  guinea-pig  169.  Died  at  9  p.  m.  the  same  day.  Exten- 
sive subcutaneous  cedema,  small  intestine  contains  a  bloody  flnid.  Bacillus  N  in 
effused  bloody  serum  (slide  1376). 

July  31,  10:30  j)-  m.— Injected  subcutaneously  into  guinea-pig  173,  3  minims  of 
bloody  serum  from  cellular  tissue  of  guinea-pig  171.    Died  at  10  a.  m.,  August  1.    Ex- 
leusive  separation  of  skin  and  softening  of  subcutaneous  tissues,  with  some  bloody 
effusion.     Small  intestine  hyperajmic  and  contains  a  bloody  fluid,  liver  rather  soft 
gall  bladder  empty,  spleen  normal. 

August  1,  12  m. — Injected  subcutaneously  into  guinea-pig  174,  3  minims  bloody 
serum  from  cellular  tissue  of  guinea-pig  173.  Found  dead  at  6  a.  m.  next  day. 
Usual  extensive  subcutaneous  a}dema  containing  bacillus  N  and  other  bacilli,  spleen 
large,  stomach  hypenemic. 

August  1,  12  m. — Injected  subcutuueously  into  guinea-pig  17.5,  4  minims  bloody 
fluid  from  intestine  of  guinea-pig  173.  Died  at  8  a.  m.,  August  2.  Extensive  soften- 
ing of  tissues  and  subcutaneous  redema,  intense  hypertemia  of  small  intestine,  spleen 
slightly  enlarged,  liver  normal  in  appearance.     Bacillus  N  in  effused  bloody  serum. 

August  d,  10  jj.  m. — Injected  subcutaneously  into  guinea-pig  18,  2  minims  from  in- 
testine of  case  SO ;  viscid  mucus,  dark  in  color,  slightly  acid.  Died  at  5  p.  m.  Ano-ust 
10.  Extensive  subcutaneous  cedema  containing  bacillus  N,  slide  1413.  Spleen  some- 
what enlarged,  liver  normal.  Bacillus  x  in  anaerobic  culture  from  effused  serum  iu 
cellular  tissue. 

August  10,  5:30  j;.  m. — Injected  subcutaneously  into  guinea-pig  1S9,  2  minims  of 
bloody  serum  from  cellular  tissue  of  guinea-pig  182.  Died  at  3  p.  m.,  Auo-ust  11. 
Very  extensive  subcutaneous  redema,  with  separation  of  skin  and  softeniu"-  of 
muscles. 

Aiigusill,  3  2>.m. — Injected  subcutaneously  into  rabbit  162,  5  minims  bloody  serum 
from  cellular  tissue  of  guinea-pig  184;  contains  bacillus  N,  etc.     Died  at  10:30  a.  m. 
August  15.  Abscess  iu  middle  of  belly,  liver  dark  in  color,  spleen  normal.  Liver  kept 
48  hours  iu  antiseptic  wrapping  contains  bacillus  N  and  other  bacilli. 

August  10,  11:30  a.  wi.— Injected  subcutaneously  into  guinea-pig  183,  2  minims 
Tiscid  mucus  of  a  brown  color  and  sightly  acid  reaction  from  intestine  of  case  31. 
Dead  at  6  a.  m.,  August  13.  Extensive  subcutaneous  cedema.  Cultures  iu  o-elatin 
from  effused  serum  contain  colon  bacillus. 

August  12,  3  j;.  m.— Injected  subcutaueously  into  guiuea-pig  187,  3  minims  material 


134     ETIOLOGY  AND  PEEVENTION  OF  YELLOW  FEVER. 

from  intestine  of  case  :)2,  black  color,  alkaline  reaction.  Animal  had  au  abscess  in 
middle  of  belly,  bat  recovered. 

JtujiistVi,  12:30  J),  w.— Injected  subcntaneously  into  guinea-pig  188,2  minims  of 
viscid,  black  material  from  intestine  case  20.  Contains  bacillus  N.  Died  at  9:30, 
August  14.  Very  extensive  subcutaneous  cedema  with  softening  of  abdominal 
muscles  and  separation  of  skin  from  abdominal  walls.     Usual  odor. 

Eemark  :  An  oftcnsive  odor  is  given  off  from  the  necrosed  tissues 
when  the  abdominal  poucU  containing  bloody  serum  is  opened.  The 
extent  of  the  disorganization  of  tissue  which  occurs,  often  in  less  than 
18  hours,  is  surprising,  and  is  evidence  of  the  great  virulence  of  this 
material  from  the  intestine. 

August  15,  2}).  m. — Injected  subcntaneously  into  rabbit  172,  2  minims  material  from 
intestine  of  case  35  (alkaline).  Dead  at  6  a.  ni.  next  day.  Liver  dark  in  color, 
contains  a  few  bacilli  and  numerous  stained  masses  (?),  slide  1438.  No  subcutaneous 
oedema.     Spleen  normal ;  bacillus  x  obtained  in  cultures  from  liver. 

August  19,  7:30.— Injected  subcutaneously  into  guinea-pig  192,  2  minims  material 
from  intestine  case  36  (acid.)  Animal  found  dead  at  6  a.  m.  next  day.  The  usual 
subcutaneous  ccdema,  with  separation  of  skin  and  softening  of  abdominal  muscles. 

August  21,  10:30  jj.  m. — Injected  subcutaneously  into  guinea-pig  195,  3  minims  vis- 
cid black  material  from  intestine  case  37.  Animal  found  dead  at  6  a.  m.,  Angust  23. 
Extensive  subcutaneous  oedema ;  contains  bacillus  N.  Softening  of  muscles  and  sep- 
aration of  skin,  liver  rather  soft,  small  intestine  contains  a  bloody  fluid.  Culture 
from  liver  contains  bacillus  x. 

Auqust  21,  2 p.  m. — Injected  subcutaneously  into  guinea-pig  196,  2  minims  viscid 
material,  not  black,  from  intestine  case  38  (acid  reaction).  Animal  dead  at  6  a.  m., 
August  24.  Subcutaneous  O'dema  not  as  prononnced  as  usual,  liver  rather  light  in 
color,  spleen  enlarged. 

MATERIAL  FROM  THE    INTESTINE    DOES    NOT   ALWAYS  KILL   GUINEA 

PIGS  AND  RABBITS. 

June  29,  1  2^.  wi. — Injected  subcutaneonsly  into  guinea-pig  125,2  minims  of  material 
from  intestine  of  case  25.     Result  negative. 

^iugust  19,  7:30  jA  m. — Injected  subcntaneously  into  rabbit  177,  3  minims  material 
from  intestine  of  case  36  (acid).     Result  negative. 

MATERIAL  FROM   THE   LIVER  AND   INTESTINE  KEPT  IN  THE  COLLECT- 
ING BULB  FOR   TWO   WEEKS   OR   MORE   LOSES   ITS  VIRULENCE. 

May  28,  4  jj.  m. — Injected  subcutaneously  into  guinea-pig  65,  2  minims  of  material 
from  intestine  case  17,  kept  in  laboratory  for  16  days  (alkaline  reaction).  Result 
negative. 

May  29,  2:30  2>.  m. — Injected  subcutaneously  into  guinea-pig  67,  2  minims  of  ma- 
terial from  intestine  case  1.5,  kept  in  laboratory  for  1  month  (alkaline  reaction).  Re- 
sult negative. 

May  30,  Zp.  m. — Injected  subcutaneously  into  guinea-pig  69,  2  minims  of  bloody 
fluid  from  collecting  bulb  containing  material  from  liver  case  18,  in  laboratory  2 
weeks.     Result  negative. 

ilfay  30,  3  jj.  w. — Injected  subcutaneously  into  guinea-pig  70,  2  minims  material 
from  intestine  case  18,  kept  in  laboratory  2  weeks,  and  now  decidedly  alkaline.  Re- 
sult negative. 

COMPARATIVE    EXPERIMENTS. 

June  6,  10  a.  m. — Injected  subcutaneously  into  guinea-pig  86,  5  minims  material 
from  .small  intestine,  case  of  heart  disease  (comparative  autopsy  No.  7);  fluid  has  a 
yellow  color  and  slightly  acid  reaction.  Animal  found  dead  next  day  at  6  a.  m. 
Subcutaneous  cedema. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  135 

June  S,  12  m. — Injected  suljcutaneonsly  into  gninea-pig  92,  3  minims  bloody  serum 
from  counective  tissue  of  guinea  pig  86.  Auimal  died  June  11  at  10  a.  ra.  No  sub- 
cutaneous oedema,  abscess  iu  middle  of  belly,  uo  microorganisms  from  liver,  ab- 
dominal viscera  normal. 

This  ended  the  series,  and  I  have  not  made  further  comparative  ex- 
periments with  material  from  this  source.  The  virulence  in  the  above 
experiments  was  decidedly  less  than  in  those  in  which  material  from 
the  intestine  of  yellow-fever  patients  has  been  injected,  inasmuch  as  the 
second  animal  in  the  series  lived  for  3  days,  and  instead  of  a  malig- 
nant and  rapidly  fatal  (sdema,  an  abscess  was  formed  in  the  walls  of 
the  abdomen. 

It  will  be  seen  from  the  experiments  quoted  that  tlie  virulence  of 
material  from  the  small  intestine  of  yellow-fever  cadavers  is  even 
greater  than  is  that  of  liver  kept  48  hours  in  an  antiseptic  wrapping. 
The  microiirganisms  encountered  in  the  animals  killed  by  such  injec- 
tions are  the  same  iu  both  cases,  a  fact  which  gives  support  to  the  in- 
ference that  the  bacilli  found  in  the  liver  came  originally  from  the  in- 
testine. And  as  the  virulence  in  liver  tissue  is  only  developed  after  the 
development  of  these  microorganisms  in  large  numbers  has  occurred,  we 
conclude  that  it  depends  upon  their  presence.  The  loss  of  virulence 
in  material  from  the  intestine  kept  for  some  time  shows  that  virulence 
is  not  due  to  ordinary  putrefactive  organisms,  but  is  destroyed  by  the 
j)utrefactive  alkaline  fermentation  which  occurs.  Most  of  the  micro- 
organisms which.  I  have  isolated  from  this  virulent  material  grow  freely 
iu  an  acid  medium,  and  some  of  them  produce  an  acid  reaction  in  cul- 
ture media  containing  glycerine  or  sugar.  My  exi^eriments  indicate 
that  the  large  anaerobic  bacillus  N  is  chiefly  concerned  in  the  produc- 
tion of  the  extensive  inflammatory  cedema  resulting  from  the  subcuta- 
neous inoculation  of  material  containing  it,  and  death  is  no  doubt  due 
to  this  local  inflammation  rather  than  to  the  invasion  of  the  blood  by 
other  bacilli  associated  with  this  strictly  anaerobic  bacillus,  which  is 
not  found  in  blood  from  the  general  circulation  or  in  the  parenchyma 
of  the  liver  and  spleen.  The  bacilli  recovered  from  the  blood  have  been 
various,  but  as  a  rule  they  have  not  been  numerous.  Those  found  most 
frequently  are  facultative  anaerobic  bacilli,  and  among  them  my  bacil- 
lus a  and  bacillus  x  have  been  the  most  constant.  Bacillus  xx,  which 
is  very  pathogenic  for  guinea  pigs,  was  obtained  in  a  series  of  animals, 
starting  from  guinea  pig  jSTo.  102,  inoculated  with  material  from  the  iu- 
testine  of  case  24.  But  this  bacillus,  in  pure  cultures,  does  not  pro- 
duce the  intense  inflammatory  cedema  which  results  from  the  injection 
of  a  little  material  from  the  intestine.  The  same  is  true  as  regards  all 
the  rest  in  the  list,  with  the  exception  of  bacillus  N;  and  my  injections 
of  cultures  containing  this,  although  they  have  commonly  caused  the 
death  of  the  animal  from  the  local  inflammatory  cedema.  havenoti)roved 
these  culture  to  be  as  intenseh^  virulent  as  is  the  material  from  the  in- 
testine or  from  liver  which  has  been  kept  for  48  hours  in  an  antisep- 


13G     ETIOLOGY  AND  PEEVENTION  OF  YELLOW  FEVER. 

tic  wrapplug.     Wbeu  associated  with  bacillus  x  the  cultures  have, 
however,  shown  very  great  virulence,  as  in  the  following  experiments : 

August  12,  1:15  jj.  m. — Injected  snbciitaueously  into  gninea-pig  186,  5  minims  of  an 
anaerobic  culture  of  bacillus  N  iu  glycerine  agar  (contains  also  bacillus  xj,  animal 
dying  at  1  p.  m.  next  day;  killed.  Very  extensive  subcutaneous  fedema,  with  sep- 
aration of  the  skin  and  softening  of  abdominal  muscles;  odor  like  that  iu  animals 
killed  directly  by  injection  of  material  from  intestine.  Bacillus  N  in  bloody  serum 
from  connective  tissue  ;  liver  rather  light  iu  color. 

August  12,  2jj.  m. — Injected  subcutaueously  into  rabbit  163,  4  minims  of  anaerobic 
culture  in  glycerine  agar  of  bacillus  N;  contains  also  bacillus  a;  (culture  from  liver 
of  case  30).  Animal  died  at  7  a.  m.,  August  15.  Extensive  subcutaneous  oedema 
coutaiuiug  bacillus  N  and  bacillus  x.    Abdominal  viscera  normal  in  appearance. 

Note. — Bacillus  aj  alone  does  not  kill  guinea-pigs  or  rabbits  when  injected  sub-, 
cutaneously.     This  is  shown  by  the  following  experiment : 

Ju)ie  13,  4  jj.  m. — Injected  subcutaueously  iuto  guinea-])ig  104-,  one-half  cubic  centi- 
metre anaerobic  culture  of  bacillus  x  iu  glycerine  agar.     Result  negative. 

Additional  experiments  with  cultures  of  these  bacilli  will  be  given 
in  connection  with  the  sj'stematic  account  of  the  various  microorgan- 
isms isolated  from  yellow-fever  cadavers. 

V-EXAMINATION  OF  TISSUES  PRESERVED  IN  ALCOHOL. 

In  all  infectious  diseases  which  have  been  proved  to  be  due  to  the 
presence  of  a  parasitic  microorganism  in  the  blood,  this  organism  may 
be  demonstrated  in  properly  stained  thin  sections  of  the  tissues.  In 
such  sections  we  often  obtain  cross  sections  of  small  blood  vessels  in 
which  the  blood  corpuscles  are  in  situ,  and  in  which  a  stained  micro- 
organism, if  present,  would  be  very  apparent.  We  also  have  a  satis- 
factory view  of  the  contents  of  the  capillary  vessels  of  the  liver,  kidney, 
brain,  etc.,  in  well-prepared  sections  of  these  organs.  Pathologists, 
therefore,  look  upon  a  careful  research,  by  the  methods  which  have 
been  perfected  with  this  object  in  view,  as  of  prime  importance  in  any 
attempt  to  i)rove  whether  a  given  infectious  disease  depends  upon  the 
presence  iu  the  blood  of  a  specific  microorganism.  Moreover,  in  cer- 
tain infectious  diseases  in  which  a  parasitic  microorganism  has  been 
proved  to  be  the  essential  etiological  factor  this  organism  is  not  found, 
as  a  rule,  iu  the  general  blood  cu-rrent,  but  is  present  in  the  tissues 
especially  implicated  iu  the  morbid  proc'ss  ;  e.  g.,  in  typhoid  fever  in 
the  spleen  and  intestinal  glands ;  in  tuberculosis,  in  the  tubercular 
nodules  in  the  lungs  and  elsewhere.  Failure  to  find  a  parasitic  organ- 
isna  in  blood  drawn  from  the  finger  is  tberefore  not  satisfactory  evi- 
dence of  the  absence  of  a  specific  germ  from  the  tissues  of  the  organs 
involved. 

As  in  yellow  fever  the  liver  and  kidneys  give  evidence  of  patholog- 
ical changes  resulting  from  this  disease.  I  have  naturally  given  spe- 
cial attention  to  these  organs  in  the  researches  I  have  made. 

The  Havana  commission  in  1879  made  numerous  sections  of  mate- 
rial preserved  iu  alcohol  from   eighteen  cases,  and  a  careful  examiua- 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER.  137 

tiou  of  these  sections  failed  to  reveal  tlie  ])reseuce  of  auy  microoroau- 
isms ;  but  as  more  satisfactory  methods  of  staining  have  since  been 
devised,  I  have  not  considered  the  work  done  at  that  time  as  conclusive 
in  this  regard. 

I  therefore  wrote  to  my  friend  Dr.  Daniel  M.  Eurgess,  of  Havana, 
sometime  during  the  summer  of  1884,  requesting  him  to  obtain  for  me 
small  pieces  of  liver,  kidney,  and  stomach  from  one  or  more  typical 
cases  of  yellow  fever.  I  made  it  an  essential  condition  that  the  autop- 
sies should  be  made  within  an  hour,  or,  at  the  outside,  2  hours  after 
death,  so  that  there  might  be  no  question  of  post-morcem  changes. 
Small  pieces  of  the  organs  named  were  to  be  put  at  once  into  a  large 
quantity  of  strong  alcohol.  In  compliance  with  my  request,  Dr.  Burgess 
obtained  and  forwarded  to  me  material  from  two  cases,  which  reached 
me  in  good  condition,  and,  upon  microscopic  examination,  the  liver  and 
kidneys  showed  the  pathological  changes  constantly  found  in  the  dis- 
ease in  question.  During  the  winter  of  1884  I  mounted  numerous  thin 
sections  from  this  material,  stained  with  various  aniline  colors.  In 
none  of  them  did  I  find  any  microorganisms,  except  upon  the  surface 
of  the  mucous  membrane  in  sections  of  the  stomach,  where  various 
organisms — bacilli  and  micrococci — were  to  be  seen  in  properly  stained 
sections.  TJiese  were,  however,  only  upon  the  surface,  attached  to  the 
epithelium,  or  mingled  with  a  granular  debris  adhering  to  the  surface 
of  the  mucous  membrane.  In  the  autumn  of  1885,  during  a  visit  to 
Dr.  Koch's  laboratory  in  Berlin,  I  had  an  opportunity  to  avail  myself 
of  the  suggestions  and  valuable  assistance  of  the  master  in  bacteriology, 
and  again  studied  the  material  which  Dr.  Burgess  had  sent  me  from 
Havana  by  the  various  methods  of  staining  considered  to  be  most 
useful  in  such  a  research.  At  the  request  of  Dr.  Koch  I  was  assisted 
in  this  research  by  Dr.  Carl  Seitz,  who  was  at  the  time  engaged  upon 
his  studies  of  the  typhoid  bacillus,  and  was  an  expert  in  staining  and 
niounting  thin  sections  of  the  tissues.  Dr.  Seitz  and  myself  examined 
numerous  sections  of  liver  and  kidney  stained  by  various  methods  with 
an  entirely  negative  result,  so  far  as  the  presence  of  microorganisms 
was  concerned.  After  my  return  to  Baltimore,  in  1886, 1  again  made 
numerous  sections  from  the  same  material,  and  stained  them  with  Loef- 
fler's  alkaline  solution  of  methylene  bine,  which  we  had  also  used  in 
Dr.  Koch's  laboratory,  and  with  other  aniline  colors,  but  without  any 
better  success. 

Desiring  to  repeat  these  researches  upon  fresh  material,  I  wrote  to 
my  friend  Dr.  Burgess,  during  my  stay  in  Rio  (Juue  and  July,  1887), 
requesting  him  again  to  collect  pathological  material  for  me  from  at 
least  four  cases  of  yellow  fever,  so  that  after  my  return  to  Baltimore  I 
might  continue  these  investigations.  As  before,  this  material  was  to 
be  obtained  as  soon  as  possible  after  death,  and  to  be  put  at  once  in 
strong  alcohol.     About  the  1st  of  December  I  received  from  Dr.  Bur- 


138  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

gess  the  desired  material  iu  good  condition,  togetber  with  the  follow- 
ing letter : 

Havana,  Xovember  19, 1887. 
My  Dear  Doctor:  I  send  yon,  per  Dr.  Spore,  of  City  of  Washhujton,  which  sails 
to-day,  one  box  of  pathological  specimens.  *  *  *  Yon  can  rely  implicitly  upon 
the  specimens  having  boon  taken  from  well-diagnosticated  yellow-fever  cases,  at 
the  time  post-mortem  stated  on  the  bottles.  All  had,  besides  the  proper  tempera- 
ture curve,  irritable  stomach,  black  vomit,  highly  albuminous  uriue,  eventually  iu 
most  cases  suppression  of  urine,  etc.     I  saw  them  repeatedly. 

The  bottles  were  marked  as  follows  : 

Case  No.  1. — Sick  from  August  14  to  19, 1887.     Autopsy  1  hour  after  death. 
Case  No.  2. — Died  September  23, 1887,  at  4:30  a.  m.     Autopsy  2-^  hours  after  death. 
Case  No.  3. — Died  October  5, 1887,2:30  a.  m.     Antopsy  15  minutes  after  death. 
Case  No.  4.— Died  October  26, 1887,  .^):30  a.  ni.     Autopsy  7  o'clock  a.  ni.,  body  still 
warm  (temperature  40°  C). 

From  tlie  above-described  material  I  bave  had  made  a  large  number 
of  very  thin  sections,  which  I  have  studied  by  various  methods  of  stain- 
ing and  with  objectives  of  high  power,  tbe  oiie-eigbteenth  and  one- 
twelfth  inch  bom.  ol.  im.  of  Zeiss.  1  bave  used  especially  tbe  alkaline 
solution  of  metbylene  bine  of  Loeffler ;  Gram's  well-known  method,  with 
methyl  violet,  followed  by  iodine  solution  and  decolorizatiou  with  al- 
cohol; tbe  metbod  of  Weigert,  which  is  the  same  as  Gram's  up  to  tbe 
point  of  removing  tbe  sections  from  the  iodine  solution,  when  they  are 
decolorized  and  debydrated  with  a  mixture  of  two  parts  of  aniline  oil  to 
one  part  of  xylol.  I  bave  been  especially  pleased  with  the  last-men- 
tioned metbod,  which  gives  fine  views  of  tbe  tissue  elements  and  any 
microorganisms  wbich  may  be  present.  I  also  stained  numerous  sec- 
tions with  fnchsin  in  solution  with  carbolic  acid  (5  per  cent.),  or  witb 
aniline  oil  (tubercle  stain),  and  with  various  other  aniline  colors. 

I  tbink  I  am  safe  in  asserting  that  all  known  pathogenic  microorgan- 
isms may  be  stained  by  one  or  more  of  the  methods  above  referred  to. 
Indeed,  the  alkaline  solution  of  metbylene  blue  is,  so  far  as  I  know,  an 
agent  wbich  stains  all  organisms  of  tbis  class,  although  tbere  are  dif- 
ferences as  to  the  rapidity  witb  which  they  stain  and  the  tenacity  with 
which  they  retain  tbe  color  imparted  to  tbem. 

Tbe  result  of  tbis  research  has  again  been  negative  so  far  as  the 
general  presence  of  any  i).aiticular  microorganism  in  tbe  materiid  exam- 
ined is  concerned.  But  in  one  case  (No.  iv)  I  found  in  tbe  kidney  a 
minute  bacillus,  which  apparently  invaded  by  preference  the  glomeruli. 
It  was  not  found  in  tbe  capillaries  generally,  but  a  certain  number  of 
foci  were  found,  some  small,  as  shown  in  Fig.  6,  and  involving  only  a 
portion  of  a  glomerulus,  others  involving  a  whole  glomerulus  and  tbe 
tissues  immediately  surrounding  it.  Tbe  appearance  was  such  as  one 
would  expect  to  see  in  a  case  in  which  solitary  bacilli,  carried  in  tbe 
first  place  by  tbe  blood  current,  had  effected  a  lodgment  and  estab- 
lished a  center  of  infection  in  tissues  already,  perhaps,  necrotic,  and 
through  wbich  the  circulation  bad  ceased.  Tbe  latter  supposition  seems 
to  be  JListihed  by  tbe  fact  that  there  were  comparatively  few  of  these 


ETIOLOGY    AND    PREVP^NTION    OF    YELLOW    FEVER.  139 

foci,  whereas  if  they  had  been  established  while  the  circulation  was 
still  going  on  we  would  expect  to  liud  numerous  secondary  foci  and  a 
certain  number  of  bacilli  iu  the  neighboring  capillary  vessels.  More- 
over, there  was  uo  evidence  of  inflammatory  reaction  as  a  result  of  this 
invasion  of  the  tissues  by  parasitic  organisms.  I  am,  therefore,  of  the 
opinion  that  this  is  some  ordinary  saprophyte  which  had  effected  a 
lodgment  in  the  kidney,  possibly  during  the  last  hours  of  life  when  the 
vital  resistance  of  the  tissues  was  slight,  or  when,  as  a  result  of  the 
blood  stasis  in  the  organ,  local  necrosis  had  already  occurred  at  certain 
points  before  death. 


Fig.  6.— Collection  of  straight  bacilli  in  glomerulus,  yellow  fever  kidney.     Material  from  Havana. 

It  is  quite  probable  that  during  the  last  hours  of  life  a  certain  num- 
ber of  microorganisms  from  the  intestine  succeed  in  passing  through 
the  enfeebled  tissues  to  the  interior  of  the  capillaries,  and  are  carried 
away  by  the  already  slowly  moving  blood  stream  to  distant  organs, 
where  they  may  establish  centers  of  growth  even  before  death  occurs, 
or  are  at  least  in  position  to  take  possession  of  the  field  as  soon  as  the 
vital  spark  has  been  extinguished.  In  the  case  in  question  I  believe 
that  the  true  explanation  of  the  presence  of  the  organisms  described  is 
that  suggested,  for  I  have  not  found  in  the  other  cases  examined  any 
similar  collection  of  bacilli,  and  can  not  therefore  attach  any  importance 
to  the  observation  so  far  as  the  etiology  of  yellow  fever  is  concerned. 
In  Berlin  I  fell  upon  a  little  group  of  minute,  slender  bacilli,  in  a  capil- 
lary of  the  liver,  and  recently  I  have  found  a  similar  group  in  a  pre- 
paration of  skin  from  a  yellow  fever  patient.  I  have  also  in  the  course 
of  my  extended  observations  seen  two  or  three  groups  of  micrococci,  or 
of  what  appeared  to  be  micrococci.    But  I  attach  no  importance  to  such 


140  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

observations.  Evidently  any  organism  concerned  in  tlie  etiology  of  an 
infectious  disease  should  be  found  not  occasionally  and  in  certain  cases 
only,  but  if  seen  at  all  by  the  staining  methods  adopted  it  should  be 
found  distributed  through  the  organs  involved  in  sufficient  numbers  to 
leave  no  doubt  as  to  its  presence,  not  as  an  accident,  but  as  a  general 
and  constant  thing  in  all  cases  of  the  disease  under  investigation. 

The  bacillus  above  described,  present  in  a  single  case,  is,  then,  the 
only  microorganism  found  in  the  material  obtained  in  Havana  in  1887 
so  far  as  the  liver  and  kidney  is  concerned.  In  my  stained  sections  of 
stomach  and  intestine  I  have  observed  various  microorganisms,  upon 
the  surface  of  the  mucous  membrane,  but  extended  researches  have 
failed  to  show  that  any  one  of  these  organisms  invades  the  living  tissues 
of  the  alimentary  canal. 

The  material  i^reserved  in  alcohol  at  my  autopsies  made  in  Havana 
in  1888  and  1889  has  also  been  carefully  studied  by  myselt  and  by  my 
laboratory  assistants.  The  results  correspond  with  those  obtained  by 
the  culture  methods  employed  in  the  same  cases.  In  those  cases  in  which 
my  cultures  gave  a  positive  result  I  have,  as  a  rule,  found  the  same  micro- 
organisms in  thin  sections  of  the  same  material — liver,  spleen,  kidney — 
])rcserved  in  alcohol. 

Thus  the  sections  from  case  9  (1888)  contain  numerous  bacilli  which 
correspond  in  their  morphology  with  the  colon  bacillus  which  was  ob- 
tained in  my  cultures  from  the  blood,  liver,  and  kidney  of  the  same  case. 
The  same  is  true  of  case  20.  In  case  14  and  in  case  33,  in  which  my  ba- 
cillus N  was  i^resent  in  smear  i^reparations  from  the  fresh  liver  tissue,  it 
is  also  present,  as  was  to  have  been  expected,  in  thin  sections  of  the 
liver  preserved  in  alcohol.  In  short,  while  the  general  result  has  been 
negative,  various  bacilli  have  been  found  in  certain  cases,  and  in  one  case 
(No.  10)  groups  of  micrococci  are  present  in  thin  sections  of  the  kidney. 

In  order  that  this  part  of  the  work  might  be  as  thorough  as  possible 
and  free  from  the  reproacli  of  jiersonal  bias  or  imperfect  technique,  I 
have  had  a  series  of  sections  made  from  twenty-live  of  my  Havana  au- 
topsies by  my  friend  Dr.  James  E.  Keeves,  of  Chattanooga,  Tenn.,  and 
have  placed  them  beside  my  own  sections  ajid  those  made  under  my 
direction  by  my  laboratory  assistant,  Br.  Emilio  Martinez.  These  slides 
will  be  transmitted  with  my  report  for  permanent  preservation  in  the 
Army  Medical  Museum. 

Further,  I  have  submitted  this  entire  series  of  slides  to  Dr.  William 
T.  Councilman,  of  the  Johns  Hopkins  University,  for  careful  study,  and 
give  below  his  report  upon  the  results  of  his  examinations: 

I  was  requested  by  Dr.  Sternberg  to  examine  the  material  which  bo  had  collected 
frotn  a  large  number  of  cases  of  yellow  fever.  This  material  was  collected  in  Harau  a 
and  in  the  South,  iu  the  epidemic  of  1888.  Sections  which  had  been  made  by  Dr. 
Reeves  in  Chattanooga,  and  under  Dr.  Sternberg's  direction  at  the  Johus  Hopkins 
University,  were  carefully  examined,  and,  in  addition,  the  material  from  thirty 
autopsies  was  given  me  by  Dr.  Sternberg  and  further  investigated  at  tlie  XJathological 
laboratory  of  the  Johns  Hopkins  Ho.spital.     Most  of  this  material  was  obtained  from 


ETIOLOGY    AXD    PREVENTION    OF    YELLOW    FEVER.  141 

fresh  autopsies  2  to  12  hours  after  death  and  was  hardeued  ia  alcohol,  only  three  of 
the  cases  examined  were  hardened  in  Muller's  fluid. 

One  hundred  and  thirty  sections  were  examined,  among  them  three  which  Dr.  .Stern- 
berg had  obtained  from  Dr.  Freire  in  Brazil.  These  sections  were  stained  with  methy- 
lene blue,  gentian  violet,  Bismarck  brown,  and  with  the  Gram  and  Weigert  methods. 
The  sections  which  were  given  Dr.  Sternberg  by  Dr.  Freire  in  Brazil  were  stained 
red,  probably  with  fuchsin.  Of  these  specimens  it  is  not  necessary  to  say  much.  It 
was  most  imi)Ossible  to  say  from  what  tissue  they  were  made,  and  to  have  recognized 
any  organisms  in  the  precipitate  of  staining  fluid  and  other  debris  would  have  been 
impossible.  The  sections  made  by  Dr.  Reeves  and  those  under  Dr.  Sternberg's  direc- 
tion were  in  general  good,  particularly  the  latter.  It  is  probable  that  these  sections 
show  clearly  all  the  bacteria  which  are  contained  in  the  tissue.s,  for  other  more  comj>li- 
cated  methodsof  staining  gave  the  same  results  as  to  bacteria.  All  of  the  bacteria  found 
were  stained  with  the  simplest  methods.  Bacteria  of  some  sort  were  found  in  28  of 
the  130  sections  examined  ;  of  these  18  were  sections  of  the  liver,  8  of  the  kidney,  and 
1  each  of  stomach  and  lymph  gland.  There  was  nothing  in  their  form  or  relation 
to  the  tissue  that  would  lead  one  to  suppose  that  their  presence  was  other  than  acci- 
dental. In  no  case  could  any  connection  be  shown  between  their  presence  and  the 
essential  lesions  of  the  disease.  There  were  both  micrococci  and  bacilli,  in  some 
cases  arranged  in  groups,  in  others  they  were  single  or  in  indefinite  masses.  In  no 
case  was  their  any  lesion  in  the  surrounding  tissue  which  could  be  attributed  to 
their  presence.  Among  the  bacilli  were  some  which  agreed  in  form  with  the  colon 
bacillus. 

The  micrococci  were  in  the  form  of  the  well-known  emboli,  and  were  found  in  the 
blood  vessels  of  the  liver  and  kidneys;  in  the  latter  generally  in  the  glomeruli.  In 
but  one  case  were  bacilli  found  in  the  tubules  of  the  kidney. 

Five  sections  of  stomach  were  examined,  but  nothing  characteristic  found  in  these. 
In  one  of  these  sections  there  was  some  evidence  of  gastritis  shown,  by  the  presence 
of  leucocytes  in  and  between  the  epithelial  cells,  and  below  the  epithelium  some 
small  cell  infiltration.     The  epithelium  was  in  general  well  preserved. 

The  sections  of  intestine,  spleen,  and  lymphatic  glands  were  perfectly  normal.  In 
one  of  the  sections  of  lyinpliatic  glands  there  were  numerous  masses  of  short  bacilli, 
which  were  also  found  in  the  other  organs  from  the  same  case.     (Case  9.) 

The  follo^ius  is  a  list  of  the  slides  which  I  propose  to  transmit  with 
this  report.  The  result  of  Dr.  Couuciloian's  careful  examination  for 
bacteria  will  be  gi^en  in  parentheses  in  every  case  where  this  result 
was  positive,    l!^o  remark  is  made  when  the  result  was  negative. 

When  no  remark  is  made  with  reference  to  the  method  of  staining 
employed,  it  will  be  understood  that  Loeffler's  alkaline  solution  of 
methylene  blue  was  the  staining  agent. 

No,  1.  Kidney  of  guinea-pig  which  died  July  23,  1837.  Mounted  by  Dr.  Domingos 
Freire  in  his  laboratory,  and  said  by  him  to  contain  his  yellow-fever 
microbe. 

2.  Section  of  kidney  of  guinea-pig  killed  on  the  16th  of  July,  1887.     Mounted  by 

Dr.  Freire,  and  said  by  him  to  contain  his  micrococcus. 

3.  Liver  of  guinea-pig  which  died  July  23,  1887.     Mounted  by  Dr.  Freire,  and 

said  by  him  to  contain  his  micrococcus. 

Note. — These  slides  are  the  only  ones  given  to  me  by  Dr.  Freire,  and 
are  placed  in  this  series  for  permanent  preservation  and  as  evidence  of 
his  microscopical  technique. 

4.  Section  of  yellow  fever  kidney,  made  in  the  laboratory  of  Dr.  Lacerda,  in  Rio 

de  Janeiro,  by  Dr.  Araujo  Goes.     Contains  the  bacillus  of  Lacerda  and 
Babes. 


142  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

No.    5.  Yellow  fever  kiduey.     Bisuiark  biowu  staiuin^i;;   .section  made  by  Dr.  Stern- 
berg in  1881. 
(3.  Yellow  fever  kidney;  metliyleuo  bine  staining.     Section  made  by  Dr.  Stern- 
berg in  1884.     Shows  unmerous  plasma  cells. 

7.  Blood   of  yellow  fever  case  in  Misericordia  Hospital,   Rio  de  Janeiro,  1887. 

Fonrtli  day  of  sickness ;  kept  in  capillary  tnbe  for  fi  d  i\  s  and  then  stained 
with  fuchsiu  by  Dr.  Sternberg. 

8.  Blood  of  yellow  fever  patient  in  small-pox  hospital,  Rio  de  Janeiro,  1887, 

Third  day  of  sickness;  stained  with  fnchsin  by  Sternberg. 
'J.  Blood  from  same  case  as  No.  8,  stained  with  osuiic  acid  and  fnchsin. 
lU.  Blood  from  yellow  fever  case  in  Misericordia  Hospital,  Rio  de  .Janeiro,  18S7. 
Fourth  day  of  sickness.     Collected  and  stained  by  Dr.  Sternberg. 

11.  Blood  of  case  of  yellow  fever  in  sniall-pox  hospital  Rio  de  .Janeiro,  1887. 

Third  day  of  sickness;  collected  and  stained  bj^  Dr.  Sternberg. 

12.  Yellow  fever  liver;  section  made  in  Dr.  Lacerda's  laboratory,  June  26,  1887, 

by  Dr.  Aranjo  Goes;  stained  with  methylene  blue  by  Dr.   Sternberg  to 
show  the  bacillus  of  Lacerda  and  Babes.     ("  Bacilli"  C.) 

13.  Yellow  fever  blood  collected  by  Dr.  Sternberg  in  Havana  in  1879.     Showing 

crystals  of  liicmatin. 

14.  Slide  from  Dr.  Carmona's  laboratory  in  the  City  of  Mexico.     Stained  and 

mountedby  Dr.  A.  Gavino.     Showing  bacilli  obtained  by  cultivation  from 
yellow  fever  urine. 

15.  Yellow  fever  blood  collected  and  dried  on  slide  in  Rio  de  Janeiro.     Stained 

with  eosiu.     Showing  eosin  "  philine  granules." 
IG.  Sections  of  intestine,  case  3,1887.     Stained  by  Gram's  method.     Numerou.s 
amorphous  stained  masses  in  intestinal  mucus  (?.) 

17.  Sections  of  stomach,  case  1,  1887.     Stained  with  carbol  fnchsin. 

18.  Sections  of  stomach,  case  1,  1887.     Stained  with  metkylene  blue.     ("A  few 

bacteria  scattered  over  the  surface"  C.) 
It).  Sections  of  stomach,  case  4,  1887.     Stained  by  Weigert's  method. 

20.  Sections  of  stomach,  case  3,  1887.     Stained  by  Gram's  method. 

21.  Sections  of  stomach,  case  4,  1887.     Stained  by  Weigert's  method. 

22.  Section  of  stonnich,  case  2,  1887.     Stained  with  methylene  blue. 

23.  Liver,  case   1,   1887.     Stained  with  Loehier's   solution   of  methylene   blue. 

("Bacilli"  C.) 

24.  Kidney,  case  1,  1887. 

25.  Kiduey,  case  1,  1887.     Weigert's  method. 

26.  Kiduey,  case  2,  1887. 

27.  Liver,  case  2,  1887. 

28.  Liver,  case  2,  1887.     Aniline  fnchsin. 

29.  Kiduey,  case  2,  1887.     Carbol  fnchsin. 

30.  Kidney,  case  3,  1887.     Aniline  fuchsiu. 
'M.  Kiduey,  case  3,  1887. 

32.  Kidney,  case  3,  1887.     ("Bacilli  in  epithelium"  C.) 

33.  Liver,  case  3,  1887. 

34.  Liver,  case  4,  1887. 

35.  Kidney,  case  4,  1887. 

36.  Kidney,  case  4,  1887. 

37.  Kidney,  case  4,  1887.     Aniline  fuchsiu. 

38.  Spleen,  case  2,  1887. 

39.  Liver,  case  2,  1887.     ( -'Leucocytic  invasion  and  bacteria"  C.) 

40.  Kidney,  case  2,  1887. 

41.  Liver,  case  3,  1887. 

42.  Liver,  case  3,  1887. 

43.  Liver,  case  3,  1887, 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVEK.  143 

No.  44.  Intestine,  case  3,  1887. 
45.  Stomach,  case  3,  1887. 
4(S.  Kidney,  case  4,  1887. 

47.  Kidney,  case  1,  1888. 

48.  Liver,  case  1,  188S. 
4U.  Kidney,  case  1,  1688. 
50.  Sjileen,  case  2,  1888. 
5).  Kidney,  case  2,  1888. 

52.  Kidney,  case  2,  1888. 

53.  Liver,  case  3,  1888. 

54.  Kidney,  case  3,  1888. 

55.  Kiduey%  case  3,  1888. 

56.  Liver,  case  3,  1888. 

57.  Kidney,  case  4,  188S. 

58.  Liver,  case  4,  1888.     ("Shows  beautiful  inflammation,  bacilli,"  C.) 

59.  Liver,  case  4,  1888. 
GO.  Kidney,  case  4,  1888. 

61.  Liver,  case  9,  1888. 

62.  Kidney,  case  9,  1888. 

63.  Liver,  case  9,  1888. 

64.  Kidney,  case  9,  1888.     ("Bacilli,"  C.) 

65.  Mesenteric  gland,  case  9,  1888.     ("Bacilli,"  C.) 

Ei<;jMAi!KS. — In  case  9,  1888,  I  ob 'aired  the  colon  bacillus  in  my  cultures 
from  the  blood,  liver,  and  kidney.  The  bacilli  present  in  stained  sections 
correspond  with  this  bacillus  in  their  morpholoj^y,  and  are  no  doubt  the 
same,  i.  e.,  the  hactcrium  coli  commune  of  Escherich. 

66.  Kidney,  case  10,  18~8.     ("Micrococci  in  vessels,"  C.) 

67.  Kidney,  case  10,  l^-SS. 

68.  Kidney,  case  10,  1888.     ("Cocci  in  vessels  aud  glomeruli,"  C.) 

Remarks. — Case  10,  1888,  is  the  only^  one  in  the  whole  scries  in  which 
micrococci  have  been  present  in  any  considerable  number.  In  this  case 
they  occur  in  the  capillaries  of  the  kidney,  in  the  form  of  "  emboli"  of  con- 
siderable size. 

69.  Liver,  case  10,  1888. 

70.  Kidney,  case  1,  1889. 

71.  Spleen,  case  1,  1889.     ("Short  bacilli,"  C.) 

72.  Liver,  case  1,  1889.     ("  Bacilli,  short  and  thick,"  C.) 

RkmaiUvS. — The  bacillus  in  this  case  is  my  bacillus  N,  which  was  found 
in  smear  preparations  from  the  fresh   liver  and  spleen,  and  obtained  in 
anaijrobic  cultures  from  the  sam-j  case. 
-73.  Kidney,  case  1,  1889. 

74.  Liver,  case  1,  1889. 

75.  Mesenteric  gland,  case  1,  1889. 

76.  Kidney,  case  2,  1889. 

77.  Liver,  case  2,  1889. 

78.  Kidney,  case  2,  1889. 

79.  Liver,  case  2,  1889. 

80.  Liver,  case  3,  1^89. 

81.  Kidney,  case  3,  1889. 

82.  Liver,  case  3,  1889. 

83.  Kiduej',  case  4,  1889. 

84.  Liver,  case  4,  1889. 

85.  Kidney,  case  4,  1889. 

86.  Liver,  case  4,  1889. 

^7.  Liver,  case  5,  1889.     ("Sliort  bacilli  in  small  numbers  in  capillaries,  in  pairs 
and  in  short  chains,"  C.) 


144  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

No.    83.  Kidney,  case  5,  1889.     ("lu  vessels  aud  glomeruli,  short  bacilli  in  pairs  and 
groups,-'  C.) 

89.  Liver,  case  5,  1889.     ("Bacilli,"  C.) 

90.  Kidney,  case  .5,  1889.     ("Bacilli,"  C.) 

Remarks. — Dr.  Councilinau's  notes  sbon'  that  lie  found  bacilli  in  all  of 
the  sections  from  this  case.  Turning  to  my  notes  relating  to  the  examina- 
tion of  fresh  material  from  the  same  case  I  tiud  the  following,  "Case  18" 
(No.  5  of  1889) :  "  Sick  5  days  ;  autopsy  2  hours  after  death.  Direct  exami- 
nation of  blood  negative ;  of  liver  a  few  small  oval  bacilli  in  pairs.  Aerobic 
gelatine  Esmarch  tube  from  blood  contains  a  few  colonies  of  bacillus  a. 
Anaerobic  agar  Esmarch  tube  from  blood  contains  nuuieroug  colonies  of 
bacillus  a,  and  of  a  short  bacillus  in  chains.  Anaerobic  agar  Esmarch 
tube  from  kidney  contains  numerous  colonies  bacillus  w.  the  same  from 
liver." 

91.  Liver,  case  7,  1889. 

92.  Liver,  case  8, 1889.     ("  Small  groups  of  short  bacilli,  and  in  one  place  micro- 

cocci in  pairs."  C.) 

Remarks. — In  this  case  my  bacillus  N  was  obtained  in  anaiirobic  cul- 
tures from  the  liver,  aud  this  is  the  bacillus  present  iu  the  section  ex- 
amined by  Dr.  Councilman. 

93.  Liver,  case  11,  1889. 

94.  Liver,  case  11,  1889. 

95.  Kidney,  case  11,  1889. 

96.  Kindey,  case  11,  1889. 

97.  Liver,  case  14,  1889. 

98.  Liver,  case  14,  1889. 

99.  Liver,  case  14,  1889.     ("Bacilli,  short  and  thick  in  capilla  ies,"  C.) 

100.  Liver,  case  16,  1889.     ("  Same  as  90,"  C.) 

Remarks. —  In  this  case  my  notes  show  that  numerous  bacilli  were 
found  in  a  smear  preparation  from  the  fresh  liver  tissue,  and  that  both, 
bacillus  a  and  bacillus  x  weie  obtained  in  my  cultures  from  fresh  liver 
tissue. 

101.  Liver,  case  17,  1689. 

102.  Liver,  case  17,  1839.      ("A  few  long  slender  single  bacilli,   and  groups  of 

short  bacilli  in  capillaries,"  C.) 

Rem.^rks. — My  cultures  from  the  liver  of  this  case  gave  the  following 
result:  "Aerobic  cultures  from  liver  contain  both  bacillus  a  aud  bacillus 
X.     Anaerobic  cultures  from  liver  bacillus  N  aud  bacillu.s  0." 

103.  Liver,  case  18,  1889. 

104.  Liver,  case  18,  1889.     ("One  group  of  rather  large  organisms,"  C.) 

105.  Liver,  case  19,  1889. 

106.  Liver,  case  19,  1889. 

107.  Liver,  case  20,  1889.     ("Short  bacilli  in  groups."  C.) 

108.  Liver,  case  20,  1889.     ("Bacilli  in  groups."  C.) 

Remarks.— In  this  case  my  bacillus  N  was  present  in  a  smear  prepara- 
tion from  the  fresh  liver  tissue,  and  "numerous  colonics  of  bacillus  a  were 
obtained  in  gelatine  Esmarch  tubes  from,  the  liver." 

109.  Liver,  case  21,  1889. 

110.  Liver,  case  21,  1839. 

111.  Liver,  case  22, 1869. 

112.  Liver,  case  22, 1889, 

113.  Liver,  case  24,  1889, 

114.  Liver,  case  24, 1889, 

115.  Liver,  case  25, 1889. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVEE.  145 

116.  Liver,  case  25, 1889. 

117.  Liver,  case  26,  1889. 

118.  Liver,  case  27, 1889. 

119.  Liver,  case  28, 1889. 

120.  Liver,  case  29, 1889. 

121.  Kidney  from  Dr.  Lacerdo's  laboratory,  containing  bacillns  of  Babes  and  La- 

cerdo.     ("  Large  numljers  of  sliort  bacilli  in  cbains,"  C.) 

S.MEAIt   PREI'ARATIOXS, 

122.  Kidney  kept  48  honrs'in  an  antiseptic  T\'rapping.     Case  1,  Havana,  1888. 

123.  Liver  kept   48  liours   in   an   antiseptic  wrapping.     Case  8,  Havana,  1889. 

124.  Liver  kept  48  hours  iu   an  antiseptic  wrapping.     Case  13,  Havana,  1889. 

125.  Liver  kept  48  hours  in  au  antiseptic  wrapping.     Case  29,  Havana,  1889. 

126.  Liver,  case  1,  Havana,  1888 ;  kept  for  48  hours  iu  antiseptic  wrapping. 

127.  Liver,  case  2,  Decatur,  1888 ;  kept  for  48  hours  iu  antiseptic  wrapping. 

128.  Liver,  ci.se  10,  Havana,  1888 ;  kept  for  48  hours  in  antiseptic  wrapping. 

129.  Liver,  case  1,  Havana,  1869  ;  kept  for  48  hours  in  antiseptic  wrapping. 

130.  Liver,  case  4,  Havana,  1889;  kept  for  48  hours  in  antiseptic  wrapping. 

131.  Liver,  case  7,  Havana,  1889  ;  kept  for  4S  hours  in  antisex>tic  wrapping. 

132.  Liver,  case  14,  Havana,  1889  ;  kept  for  48  hours  in  antiseptic  wrapping. 

133.  Liver,  case  21,  Havana,  1889  ;  kept  for  48  hours  in  antiseptic  wrapping. 

134.  Liver,  case  29,  Havana,  1889  ;  kept  for  48  hours  in  antiseptic  wrapping. 

135.  Contents  of  intestine,  case  1,  Havana,  1888. 

136.  Contents  of  intestine,  case  2,  Decatur,  1838. 

137.  Contents  of  intestine,  case  3,  Decatur,  1888. 

138.  Contents  of  intestine,  case  1,  Decatur,  1888. 

139.  Contents  of  intestine,  case  2,  Decatur,  1888. 

140.  Feces,  case  1,  Decatur,  1888,  48  hours  sick. 

141.  Feces,  case  2,  Decatur,  60  hours  sick. 

142.  Feces,  case  5,  Decatur,  36  hours  sick. 

143.  Feces,  case  6,  Decatur,  48  hours  sick. 

144.  Feces,  case  7,  Decatur,  4  hours  sick. 

145.  Feces,  case  8,  Decatur,  24  hours  sick. 

146.  Feces,  case  9,  Decatur,  24  hours  sick. 

147.  Coutents  of  intestine,  case  4,  Havana,  1889. 

148.  Contents  of  intestine,  case  5,  Havana,  1889. 

149.  Contents  of  intestine,  case  9,  Havana,  1889. 

150.  Contents  of  intestine,  case  11,  Havana,  1889. 

151.  Contents  of  intestine,  case  8,  Havana,  1889. 

152.  Coutents  of  inte«tine,  case  15,  Havana,  1889. 

153.  Contents  of  intestine,  case  22,  Havana,  1689. 

154.  Contents  of  stomach,  case  2,  Havana,  1889. 

155.  Contents  of  stomach,  case  4,  Havana,  1889. 

156.  Contents  of  stomach,  case  9,  Havana,  1889. 

157.  Contents  of  stomach,  case  11,  Havana,  1889. 

158.  Contents  of  stomach,  case  13,  Havana,  1889. 

159.  Contents  of  stomach,  case  14,  Havana,  1889. 

160.  Black  vomit,  typical,  acid,  reaction,  seventh  day  of  sickness,  used  to  inocu- 

late guinea  pig  105. 

161.  Black  vomit,  typical,  acid  reaction,  used  to  inoculate  guinea  pig  88. 

162  to  No.  180.  Sections  of  yellow-fever  liver  and  kidney,  series  of  1889.     Mounted 
by  Dr.  William  T.  Councilman.     Double  stained  with  eosiue  and  methy- 
line  blue. 
4067 10 


146  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

PATHOLOGICAL   ANATOMY   AND   HISTOLOGY. 

I  shall  iutrodnce  bere  that  portion  of  my  article  contributed  to 
"  Wood's  Handbook  of  tlie  Medical  Sciences"  wbicli  relates  to  tbe  pathol- 
ogy of  tbe  disease : 

The  exterior  of  the  body  of  an  iudividiial  who  has  recently  succnnihed  to  yellow 
fever  presents  an  appearance  "which  is  quite  characteristic.  The  icteric  color  of  the 
slciu,  althonj^h  often  not  noticeable  dnring  the  last  hours  of  life,  is  developed  in  a 
large  majority  of  the  cases  very  soou  after  death.  The  color  is  that  which  is  seen  to 
follow  a  bruise  in  which  there  has  been  an  eft'usiou  of  blood,  and  the  origin  of  the 
pigment  is  no  doubt  the  same.  The  icterus  from  bile  pigments,  which  occurs  not 
infrequently  during  convalescence,  and.  which  may  be  seen  in  cases  fatal  from  a  re- 
lapse or  at  a  late  period  of  the  disease,  gives  a  uniform  saffron-yellow  color  to  the 
surface  of  the  body  and  coiijuuctivie.  In  the  icteric  discoloration  of  which  we  speak 
at  present  the  color  is  not  so  intense  and  not  so  uniformly  distributed.  The  depend- 
ing portions  of  the  body  and  especially  those  subjected  to  pressure  have  a  deeper 
coloration,  and  are  more  or  loss  livid  and  mottled  from  hypostatic  congestion. 
Dutrouleau  has  shown  that  this  ecchymotic  appearance  of  the  back  is  due  to  position 
aud  pressure  by  placing  the  body  upon  the  abdomen  or  side.  In  this  case  it  is  still 
the  most  dependent  part  which  shows  the  livid  marbled  appeaiance  referred  to.  The 
face  and  hands  frequently  appear  cyanosed,  or  the  face  may  be  livid  aud  turgesceut, 
like  that  of  one  recently  drowned.  A  little  stream  of  black  vomit  is  frequently  seen 
trickling  down  from  the  corners  of  the  mouth,  or  a  similar  fluid  may  escape  from  the 
nostrils,  and  the  lips  and  gums  may  be  soiled  Avith  dark  blood  which  has  oozed  from 
them. 

Cadaveric  rigidity  is  quickly  established  and  well  marked. 

The  api>earances  observed  upon  removing  the  calvarium  are  usually  those  of 
hyperaemia  of  the  hrain  and  its  meninges.  The  pia  niater  is  almost  always  congested 
and  the  vessels  of  the  brain  are  abnormally  full  of  blood;  the  pons  aud  medulla  are 
especially  in  a  condition  of  hyper;iMiiia.  There  is  more  or  less  effusion  into  the  sub- 
arachnoid space  and  in  the  ventricles;  this  is  sometimes  turbid  and  has  a  yellow  color. 
The  surface  of  the  brain  presents  sometimes  little  luemonhagic  points,  and  its  sub- 
stance, like  the  tissues  of  the  body  generally,  has  a  more  or  loss  pronounced  yellow 
tinge. 

Dr.  Schmidt,  of  New  Orleans,  has  described  certain  pathological  changes  in  the 
aympathetiG  (janglia  which  he  believes  to  be  important.  In  a  nuijority  of  the  cases 
examined  by  him  the  minute  blood  vessels  of  the  ganglia  were  found  to  be  tilled  with 
blood  corpuscles.  "In  two  cases  the  ganglionic  bodies  of  the  first  thoracic  as  well 
as  of  the  semilunar  ganglion  had  most  obviously  undergone  degeneration.  In  the 
greater  part  of  these  ganglion  cells  the  nuclei  had  entirely  disappeared,  leaving  no 
other  trace  but  their  nucleoli,  which  were  very  distinct;  in  the  rest  very  faint  out- 
lines of  the  nuclei  could  still  be  observed.  The  bodies  of  all  these  ganglion  cells  pre- 
sented an  indistinct  appearance,  and  were  characterized  by  a  j)eculiar  fatty  luster, 
even  observed  in  specimens  mounted  in  Canada  balsam." 

Usually  the  lungs  present  no  evidence  of  pathological  changes;  occasionally  they 
are  congested  and  contain  hemorrhagic  infarctions. 

The  fluid  in  fhe pericwrdmm  is  often  increased  in  amount  and  has  a  yellow  color;  in 
rare  cases  it  contains  blood.  The  lieart  is  commonly  paler  than  normal,  aud  accord- 
ing to  some  authors  is  often  soft  and  friable,  owing  to  fatty  degeneration  of  its 
muscular  tissue  (Riddel  Schmidt).  This  is  denied  by  others  (Crevaux,  Guiteras, 
Gania  Lobo).  Woodward,  who  examined  the  material  brought  back  by  the  Havana 
Commission  of  1879,  agrees  with  Guiteras  that  his  sections  did  not  present  any 
decided  evidence  of  fatty  degeneration,  but  remarks :  "This  by  no  means  proves  that 
it  does  not  occur  in  certain  cases,  x>erhaps  in  certain  groups  of  cases." 


ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER     147 

Several  of  the  most  coiiipeteut  observers  agree  that  there  is  a  fattj'  degeneration  of 
the  walls  of  the  small  blood  ves>iels  aud  capiUaries  of  the  various  organs,  and  account 
in  this  way  for  the  h;emorrhagic  tendency  of  the  disease.  This  is  certainly  a  more 
rational  explanation  than  the  one  so  frequently  oft'ered,  viz,  that  the  hiemorrhages 
are  due  to  the  disorganized  aud  dilHueut  condition  of  the  hlood.  A  moment's  reflec- 
tion should  show  that  this  explanation  is  insufficient,  and  that  the  hlood,  however 
diffluent,  can  not  escape  so  long  as  the  vessels  are  intact.  Ecchyniotic  points  or 
hfcmorrhagic  infractions  are  sometimes  found  upon  the  surface  or  in  the  substance 
of  the  heart,  as  well  as  in  other  muscles  of  the  body  and  the  organs  geuerally.  The 
cavities  of  the  right  side  of  the  heart  usuall}'  contain  soft  coagula  or  dark-colored 
fluid  blood,  and  the  right  ventricle  sometimes  contains  a  more  or  less  decolorized 
fibrinous  clot. 

The  t?oo(Z  in  yellow  fever  has  been  described  by  many  observers  as  "completely 
disorganized"  as  to  its  histological  elements.  This  is  a  mistake,  as  is  shown  by  the 
numerous  photomicrographs  made  by  the  writer  while  in  Havana,  in  1879,  from  the 
blood  of  cases  near  a  fatal  termination.  Both  the  red  and  the  white  corpuscles  retain 
their  normal  appearance,  and  I  have  frequently  seen  the  leucocytes  undergoing  their 
characteristic  movements,  even  after  24  hours,  in  blood  which  had  been  preserved  in 
culture  cells.  In  the  days  of  bleeding  numerous  observers  mentioned  the  fact  that 
the  blood  does  not  coagulate  readily,  or  it  forms  a  soft,  loose  coagulum  from  which  the 
serum  does  not  separate.  The  same  is  true  of  the  blood  in  the  heart  and  large  vessels 
after  death  ;  it  is  fluid  and  dark  colored.  Although  there  is  no  general  destruction  of 
the  red  corpuscles,  it  is  x^robable  that  a  considerable  number  of  these  elements  perish 
in  severe  cases,  for  the  serum  contains  free  haemoglobin,  which  gives  it  a  yellow  color 
even  as  early  as  the  third  or  fourth  day.  This  yellow  color  is  seen  in  the  serum  ob- 
tained from  the  application  of  blisters  to  the  surface,  aud  in  blood  drawn  for  micro- 
scopical examination.  In  blood  obtained  near  the  termination  of  a  fatal  case,  and  in 
Ijost-mortem  blood,  this  color  is  very  x:)rouounced,  aud  increases  in  intensity  by  further 
solution  of  the  ha-moglobin  when  the  specimen  is  kept  for  a  time;  in  the  meantime 
the  blood  disks  become  iialer  than  normal.  In  specimens  kejit  in  culture  cells  I  have 
observed  the  formation  of  beautiful  crystals  of  hEematoidin.  This  passing  of  the 
luemoglobin  into  the  serum,  w^hich  is  no  doubt  the  cause  of  the  yellow  discoloration 
of  the  tissues  in  yellow  fever,  has  been  ascribed  to  the  presence  of  bile.  This  view  is 
not  sustained  by  the  chemical  researches  of  Cunisset,  a  recent  French  author, who  has 
arrived  at  the  following  conclusions: 

"  Yellow  fever  is  not  a  poisoning  by  the  bile ;  at  the  outset  of  the  malady  the  biliarv 
pigments  are  rarelj'  found  in  the  blood  or  in  the  urine.  They  appear  generally  only 
during  the  second  i^eriod,  aud  in  a  great  number  of  cases  they  are  not  to  be  found 
at  all, 

"  The  biliary  salts,  of  which  the  powerful  action  of  '  deglobulizatiou  '  admitted  by 
certain  authors  might  exx)lain  the  disorders  which  the  maladj'^  presents,  do  not  exist 
either  in  the  matters  vomited  or  in  the  urine  or  in  the  blood  except  in  certain  cases 
in  very  feeble  quantity.  In  view  of  the  i:)rofouud  alterations  of  the  liver,  this  absence 
of  the  biliary  salts  is  easily  understood,  and  the  defective  depuration  of  the  blood  is 
to  be  looked  upon  as  a  complication  rather  than  a  determining  cause  of  the  malady." 

Schmidt  says :  "  The  icterus  in  yellow  fever  is  not  owing  to  the  presence  of  bile  in 
the  blood,  as  is  believed  by  a  large  number  of  physicians,  but  to  the  presence  of  free 
haemoglobin,  and  reiiresents  in  truth  tlie  so-called  'hiematogenous'  jaundice.  A 
'  hepatogenous  'jaundice  can  not  take  place,  as  the  larger  as  well  as  the  smaller  hepa  tic 
ducts  are  found  perfectly  open,  and  as  the  secretion  of  bile  during  the  disease,  in  the 
majority  of  cases,  is  rather  diminished,  or  even  susi^euded." 

The  white  blood  corpuscles  have  seemed  to  the  writer  to  be  rather  reduced  iunum- 
her  toward  the  end  of  fatal  cases.  In  specimens  of  blood  mounted  dry  for  microscop- 
ical examination  they  are  frequently  seen  to  contain  one  or  more  highly  refractive 
granules,  the  exact  nature  of  which  has  not  been  determined,  but  which  Isupjjose  to 


1'48  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

be  fat.  There  are  uo  microorganisms  iiresent  in  the  bhiod  of  yellow  fever  demonstrable 
bj'  the  usual  methods  of  staiuiug  and  microscopical  examination,  or  by  cultivation 
in  the  media  commonly  employed  bj^  bacteriologists. 

The  most  important  pathological  changes  in  yellow  fever  are  found  in  the  organs 
contained  in  the  cavity  of  the  abdomen.  The  mucous  membrane  of  the  stomach  is 
always  fouud  to  be  more  or  less  hypt;r;i'niic ;  the  congestion  is  commonly  not  gen- 
er?l,  but  is  confined  to  smaller  or  larger  spots  or  districts,  in  which  it  is  observed  to 
jjroceed  from  one  or  more  centers.  From  these  centers  it  extends  or  radiates  in  a 
lesser  degree,  either  gradually  to  be  lost  or  to  pass  over  to  auother  congested  district. 
It  is  owing  to  this  peculiarity  of  the  congestion  that  it  presents  no  uniformity  of 
character,  but  is  observed  to  spread  irregularly  over  larger  or  smaller  portions  of  the 
membrane  (Schmidt).  In  addition  to  these  congested  patches,  there  are  often  to  be 
seen  small  red  patches  resembling  ecchymoses,  but  which,  according  to  Schmidt, 
consist  of  "  an  unbroken  network  of  minute  vessels  congested  with  blood  and  iden- 
tical with  that  network  of  large  capillaries  which  sirrrounds  the  aperture  of  the  gas- 
tric glands."  Crevaux  believes  that  a  fatty  degeneration  of  the  cells  which  line  the 
gastric  glands  and  the  capillaries  of  the  mncous  membrane  is  the  most  important 
lesion  here.  Other  authors  speak  of  an  acute  gastric  catarrh  as  the  process  indicated 
by  the  appearance  and  histological  examination  of  the  mucous  membrane ;  others 
again  deny  that  there  is  any  inflammation.  My  own  examination  of  thin  sections 
stained  in  various  ways  shows  that  in  a  certain  proportion  of  the  cases  there  is  evi- 
dence of  inflammation,  as  shown  by  the  presence  of  an  unusual  number  of  leucocytes 
in  the  submucous  coat. 

It  has  been  asserted  that  the  epithelium  of  the  stomach  undergoes  fatty  degenera- 
tion. This  is  denied  by  Schmidt.  The  dark  fluid  so  often  ejected  during  the  last 
hours  of  life  known  as  Mack  vomit  is  almost  always  present  in.  the  stomach  in  greater 
or  less  amount  after  death.  There  is  no  question  that  the  dark  color  is  due  to  the 
presence  of  blood  pigment,  more  or  less  changed  by  the  acid  secretions  of  the  stom- 
ach. The  best  authorities  everywhere  are  in  accord  on  this  point,  which  has,  how- 
ever, recently  been  called  in  question  by  Carmona,  Freire,  and  Gibier.  These  gen- 
tlemen suppose  the  black  jtigment  to  be  a  product  produced  by  the  vital  processes 
of  a  specific  microorganism.  The  two  first-named  authors  base  their  opinion,  that 
that  the  color  is  not  due  to  blood  pigment,  upon  the  negative  results  of  their  spectro- 
scopic experiments.  Dantec  remarks,  with  reference  to  this:  "Everyone  knows 
that  the  derivatives  of  hiemoglobin  (hemapheiue,  liematine,  etc.)  are  insoluble  in 
water  ;  it  is  then  not  astonishing  that  Messrs.  Domiugos,  Freire,  and  Carmona  have 
not  obtained  any  spectroscopic  result,  since  the  first  condition  is  to  examine  the  body 
in  a  liquid  state.  Upon  dissolving  the  black  matter  with  acidified  alcohol,  we  have 
always  obtained  positive  results." 

The  author  just  quoted  has  repeated  an  experiment  often  made  in  this  country,  at 
a  time  when  the  question  was  whether  the  vomited  matter  consisted  of  "black  bile" 
or  derived  its  color  from  the  blood.  By  adding  some  drops  of  hydrochloric  acid  to 
blood  diluted  with  water,  Dantec  produced  an  "artificial  black  vomit,"  which 
resembled  exactly  that  ejected  from  the  stomach  of  yellow-fever  patients. 

The  small  intestine  commonly  contains  uujre  or  less  black  matter,  either  fluid  and 
resembling  that  found  in  the  stomach,  or  mixed  with  mucus  and  smeared  over  the 
mncous  coating,  especially  of  the  ileum.  This,  no  doubt,  comes  partly'  from  the 
stomach,  but  in  other  cases  is  due  to  passive  hemorrhage  from  the  mucous  membrane 
of  the  intestine  itself.  This  membrane  presents  arborescent  patches  of  congestion,  or 
portions  of  the  canal  may  be  uniformly  red  from  hyperasmia  of  the  mucous  coat ;  the 
color  varies  from  pale  red  to  a  reddish  brown,  and  is  usually  more  marked  in  the 
lower  portion  of  the  ileum  than  elsewhere.  The  large  intestine  occasionally  presents 
similar  arborescent  patches  of  congestion,  but  usually  it  has  .a  normal  appearance. 
Finally,  we  may  say  that  the  attention  of  pathologists  has  heretofore  been  so  largely 
taken  up  with  the  pathological  histology  of  the  organs  which  present  the  most  nota- 
ble changes — liver  and  kidney — that  the  histology  of  the  alimentary  canal  has  been 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  149 

somewhat  neglected,  and  farther  researches  in  this  direction  are  desirable  upon  ma- 
terial obtained  at  the  earliest  possible  moment  after,  death. 

The  appearance  of  the  liver  in  yellow  fester  is  characteristic,  at  least  so  far  as  acute 
febrile  diseases  are  concerned.     Usually  it  contains  less  blood  than  iu  the  normal  con- 


FiR.  7.— Patty  infiltration  of  the  liver  cells,  "svith  a  moderate  amount  of  small-celled  infiltration,  in  a 
case  of  yellow  fever.    Material  from  Havana. 

ditlon,  and  is  of  a  pale  yellow  or  brownish  yellow  color,  similar  to  that  of  new 
leather  in  its  various  shades;  occasionally  it  is  gorged  with  blood,  and  livid,  deep 
blue,  or  dark  purple  iu  color.  In  the  victims  of  chronic  alcoholism,  it  often  presents 
the  nutmeg  appearance  of  cirrhosis.  The  dimensions  do  not  differ  materially  f:om 
the  normal,  but  the  consistence  is  modified  by  the  fatty  change,  which  gives  the 
characteristic  color,  and  the  parenchyma  is  easily  torn  and  more  or  le.ss  friable.  On 
section  it  is  found  to  be  drier  than  in  the  normal  state,  except  in  the  comparatively 
few  cases  in  which  it  is  hyper;emic;  these  arc,  as  a  rnle,  cases  which  have  proved 
fatal  at  a  very  early  period — a  fact  which  indicates  that  there  is  a  stage  of  conges- 
tion antedating  that  of  au;emia  and  fatty  degeneration.  According  to  Crevaux,  this 
congestion  is  located  especially  in  the  portal  radicles  surrounding  the  lobules,  and  is 
attended  with  cedema  of  the  interlobular  connective  tissue.  Whether  this  primary 
congestion  is  a  constant  phenomenon  or  not,  it  is  certain  that  in  a  majority  of  the  au- 
topsies the  liver  is  found  to  be  anajmic,  and  to  present  more  or  less  evidence  of  fatty 
change  iu  the  hepatic  cells.  This  is  not,  however,  a  uniform  proces.s,  but  areas  of 
greater  or  less  extent  are  seen,  iu  which  the  cells  are  infiltrated  with  fat  globules,  as 
seen  in  Fig.  — ;  while  in  other  places  the  cells  appear  normal.  The  fatty  cells  con- 
tain one  or  several  fat  globules  of  varying  dimensions,  and  the  protoplasm  is  reduced 
iu  quautity  according  to  the  extent  of  this  fatty  change.  The  nuclei  very  often  re- 
main intact  in  the  cells  infiltrated  with  fat,  but  according  to  Schmidt  "a  great  num- 
ber ofthe  nuclei  also  undergo  fatty  degeneration."  Often  a  collar  of  normal  cells  re- 
mains about  the  central  vein,  while  those  cells  nearer  the  periphery  of  the  lobnle  con- 
tain numerous  fat  globules. 

In  two  of  the  livers  brought  back  from  Havana  by  the  Yellow   Fever  Commission 
of  1879,  in  which  there  was  evidence  of  cirrhosis.  Woodward  found  that,  in  addition 


150 


ETIOLOGY   AND    PREVENTION    OF    YELLOW    FEVER. 


to  the  fatty  change  described,  "an  abiiudant  infiltration  of  cells  resembling  lenco- 
cytes  was  observed,  not  merely  in  the  abnormally  developed  interlobular  connective 
tissue,  but  also  in  tlie  parenchyma  of  the  lobules."  I  have  also  found  an  infiltration 
of  leucocytes  in  two  out  of  four  cases,  which  I  have  recently  studied  with  care.  In 
one,  from  Avhich  Fig.  —  was  drawn,  it  was  attended  with  the  usual  fatty  change. 
In  the  other  it  is  far  more  pronounced,  and  the  liver  cells  to  a  considerable  extent 
are  atrophied,  and  have  lost  both  their  nucleus  and  their  protoplasm,  indeed  a  ver- 
itable necrosis  of  the  cells  has  taken  i^lace  (see  Fig.  8.)  This,  however,  is  quite  an 
exceptional  picture,  and  probably  represents  a  complication   rather  than  an  exag- 


FiG.  8.— Acnte  hepatitis,  witli  necrosis  of  the  liver  cells  (a  rare  condition). 

fever.    Havana,  1887. 


From  a  case  of  vellow 


gerated  degree  of  an  inflammation  common  to  the  disease.     Schmidt  states  that  he 
has  never  observed  any  evidence  of  iullammatiou  in  the  liver  of  yellow  fever. 

The  kidneys  are  also  the  seat  of  important  pathological  cliauges  in  the  disease  under 
consideration.  This  consists  essentiallj^  in  a  parenchymatous  nephritis.  Externally 
no  material  change  is  noted  in  the  organs.  They  do  not  vary  greatly  from  the  normal 
size,  and  usually  are  normal  in  appearance.  When  the  attack  has  been  brief,  how- 
ever, they  may  be  hyperajmic  and  of  a  deep  red  color.  Crevaux  believes  that  the 
changes  found  in  the  parenchyma  of  the  organ  are  usually  preceded  by  a  stage  of 
congestion;  Schmidt  agrees  with  him,  and  states  that  he  has  met  with  a  limited 
number  of  cases  in  which  death  had  occurred  during  this  stage  of  hypencmia.  Ec- 
chymosed  spots  and  hemorrhagic  foci  are  frequently  seen  beneath  the  capsule  or  in 
the  cortical  substance.  In  the  latter  situation  little  globular  hemorrhagic  points, 
the  size  of  a  pin's  head,  have  been  observed  which,  upon  examination,  proved  to  be 
the  distended  capsules  of  the  glomeruli.  The  change  in  the  renal  epithelium  consists 
in  a  cloudy  swelling,  followed  by  fatty  degeneration  and  desquamation.  Every  grade 
of  change  may  be  seen  in  the  same  section,  from  a  slight  degree  of  cloudy  swelling 
to  comjdete  disorganization  and  desquamation  of  the  cells.  Whole  bundles  of  tubes 
may  often  be  seen  which  have  been  stripped  of  their  epithelium  and  are  entirely 
empty.  In  thin  sections  the  lumen  of  the  tubules  is  seen  in  places  to  be  filled  with 
Infarctions  of  various  appearance.     Some  are  homogeneous  and  translucent,  and  it 


ETIOLOGY   AND    PREVENTION    OF    YELLOW    FEVER. 


151 


may  be  more  or  less  colored  witli  blood  pigment;  tbese  are  corai)osed  of  an  albumin- 
0118  material.  Otber  infarctions  are  formed  of  tbe  granular  ddbris  of  the  renal  epithe- 
lium ;  or  we  may  have  a  mixture  of  the  granular  aud  albuminous  material,  in  which 
case  the  latter  forms  a  matrix  in  AThich  the  granules  are  imbedded.  These  infarc- 
tions correspond  with  the  casts  foimd  in  the  nriue ;  those  of  a  granular  character  are 
most  abundant,  and  in  them  the  granules  often  have  a  fatty  appearance.  There  are 
also  accumulations  which  dilfer  from  these  in  the  fact  that  they  are  deeply  stained 
by  the  aniline  colors.  They  seem  to  be  made  up  of  the  nuclei  of  the  cells,  sometimes 
intact,  although  swollen  and  compressed ;  more  commonly  massed  together,  or  broken 
into  regular  fragments.  At  least  this  seems  to  be  the  most  probable  interpretation  of 
those  infarctions  which  are  stained  by  nuclear  staining  agents. 


Fig.  9. — Acute  parencliyraatous  nephritis,    a,  hyaline;  b,  granular  infarction.    From  a  case  of  yellow 

fever.    Havana,  1887. 

The  supra-renal  bodies,  according  to  Schmidt,  undergo  pathological  changes  simi- 
lar to  those  observed  in  other  organs,  "  consisting  in  the  infiltration  of  fat  aud 
hieraoglobin,  derived  from  the  blood,  and  preceded  by  hypertemia  of  the  organ.  * 
*  *  The  infiltration  or  extravasation  of  hiemoglobin  absorbed  by  the  cells  is  greater 
and  more  general  here  than  has  been  observed  in  any  other  organ.  Almost  in  every 
case  examined  it  involved  the  whole  medullary  substance,  from  which  it  extended 
into  the  inner  and  middle  layer,  sometimes  even  into  portions  of  the  outer  layer  of 
the  cortical  substance.  The  degree  of  this  pigmented  infiltration  is  sufficiently  great 
to  be  always  distinguished  by  its  brown  color  in  sections  of  fresh  specimens ;  in  some 
cases,  even,  it  appears  dark  brown. 

The  spleen  does  not  undergo  any  marked  alteration  in  yellow  fever. 

Dr.  William  T.  Councilman  has  o-i\7eii  me  the  following'  report  npoii 
the  i)athological  histology  of  the  disease,  as  shown  by  the  series  of 
slides  submitted  to  h\\n  for  examination  : 


REPORT   OF    DR.    WILLIAM   T.    COUNCILMAN. 


The  most  interesting  results  were  obtained  from  the  examination  of  the  liver.     It 
has  long  been  held  that  fatty  degeneration  of  this  organ  was  one  of  the  most  charac- 


152     ETIOLOGY  AND  PEEVEXTION  OF  YELLOW  FEVER. 

teristic  lesions  of  yellow  fever,  and  it  wasfoundto  agreateror  less  extent  iu  all  of  the 
sections  examined.  It  varied  greatly  iu  intensity  in  the  different  cases;  in  some 
comparatively  large  areas  of  liver  tissue,  which  showed  very  little  degeneration,  were 
found,  iu  others  only  here  and  there  a  few  normal  liver  cells  were  seen.  This  lesion, 
however,  does  not  seem  to  me  to  be  the  most  important  one  of  the  organ.  "When  sec- 
tions of  the  liver  are  deeply  stained  with  eosin  and  subsequently  with  a  nuclear  stain, 
either  liaematoxyliu  or  methyliue  blue,  a  very  peculiar  appearance  results.  When 
such  sections  are  examined  with  a  low  power  the  liver  cells  are  found  to  be  stained 
a  faint  reddish  blue  or  purple  color,  the  nuclei  being  a  deep  blue  or  purple.  Among 
the  liver  cells  or  in  place  of  them  a  great  number  of  bodies  stained  intensely  red 
with  the  eosin  arc  found  when  examined  with  a  high  power.  These  bodies  are  found 
to  differ  entirely  from  the  liver  cells.  They  are  sharply  circumscribed,  are  highly 
refractive,  and  are  composed  of  a  perfectly  hyaline  mass  containing  numerous 
vacuoles.  Their  size  varies  greatly  ;  in  some  cases  they  are  no  larger  than  a  leuco- 
cyte, in  others  as  large  as  two  liver  cells.  They  are  found  inclosed  in  liver  cells, 
otherwise  perfectly  normal,  and  in  some  cases  they  entirely  take  the  place  of  these  iu 
the  liver  beam- woric  between  the  capillaries.  In  some  cases  examined  they  appar- 
ently made  np  the  mass  of  the  tissue,  only  here  and  there  a  portion  of  a  liver  cell  or 
a  nucleus  of  such  being  seen.  Sometimes,  especially  where  the  liver  tissue  was  most 
scanty,  along  with  these  definite  circumscribed  masses  more  or  less  granular  material 
was  found  which  stained  in  the  same  way.  These  bodies  were  generally  round  or 
more  or  less  irregular  in  form.  In  some  of  the  liver  cells  small  hyaline  masses  stain- 
ing in  the  same  way  were  found  which  were  not  so  sharply  circumscribed  as  the  larger 
bodies.  They  were  found  most  abundantly  in  the  cases  where  the  fatty  degeneration 
was  most  extreme,  but  the  most  striking  pictures  were  obtained  where  the  liver  was 
least  altered. 

In  a  few  instances  liver  cells  were  found  which  only  differed  from  the  normal  in 
being  more  coarsely  granular,  .the  granules  staining  with  eosin  but  not  so  distinctly 
as  the  eosin  staining  bodies,  and  the  nucleus  stained  more  faintly  blue  than  the 
nuclei  of  the  surrounding  liver  cells.  In  most  cases  these  bodies  were  without  any 
nucleus;  in  others  a  nucleus  was  jiresent.  This  always  was  at  the  jjeriphery,  and  gen- 
erally took  the  long  irregular  form  of  the  nucleus  of  a  wandering  leucocyte.  Poly- 
nuclear  leucocytes  were  numerous  in  all  the  livers  examined.  Iu  some  cases  there 
were  well-defined  groups  of  them  in  the  capillaries  and  in  the  liver  beam-work  be- 
tween, and  as  it  seemed  often  in  the  red-stained  bodies.  In  several  specimens  there 
were  hemorrhages  in  the  liver,  large  areas  being  occupied  by  red  blood  corpuscles 
between  which  the  red  bodies  were  often  seen.  This  peculiar  condition  of  the  liver 
is  possibly  made  more  clear  by  staining  the  sections  deeply  with  picro-carraine.  In 
sections  so  treated  these  bodies  stain  an  intense  bright  yellow  with  the  picric  acid. 
Concerning  the  nature  of  these  bodies  there  can  be  little  question.  When  first  seen 
it  was  thought  that  they  were  probably  some  form  of  lower  organisms,  possibly 
amoibea,  but  a  more  extended  study  showed  that  this  could  not  be  so.  Bodies  in  all 
respects  similar  to  them  were  found  in  rapidly  advancing  cases  of  cirrhosis  of  the 
liver,  iu  phosphorous  poisoning,  and  in  other  cases  of  rapid  fatty  degeneration,  but 
they  are  particularly  found  iu  cases  of  acute  yellow  atrophy  of  the  liver.  Areas  were 
found  in  sections  from  this  which  were  very  similar  to  the  advanced  cases  of  yellow- 
fever  liver.  It  must  be  considered  that  in  yellow  fever,  along  with  the  fatty  degen- 
eration, there  is  a  necrosis  of  the  liver  cells  which  sometimes  affects  only  portions  of 
the  cells;  at  others  the  entire  cell.  Almost  every  change  leading  up  to  the  forma- 
tion of  these  bodies  could  be  seen.  The  exact  relation  of  the  fatty  degeneration  to 
the  necrosis  could  not  be  determiued.  The  necrotic  masses  were  found  both  in  intact 
liver  cells  and  in  those  which  had  undergone  fatty  degeneration.  In  the  latter  cases 
it  seemed  probable  that  the  necrosis  preceded,  or  at  least  accompanied,  the  degenera- 
tion. If  it  only  represented  a  necrosis  of  the  small  remnant  of  cell  protoplasm  be- 
tween the  fat  drojis  it  is  difficult  to  see  how  so  large  a  body  could  be  formed  from 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  153 

tins.  When  the  necrotic  masses  were  found  iu  the  liver  cells  they  were  nearly  always 
at  the  periphery  of  the  cell  nest  to  the  capillary. 

Aithongh  these  necrotic  masses  were  generally  found  in  the  heani-work  of  liver 
cells,  careful  examination  showed  them  frequently  to  he  in  the  hepatic  veins  and  iu 
the  capillaries.  It  would  have  heeu  interesting  to  have  examined  sections  of  the 
Inngs  to  determine  what  part  thej'  might  play  in  the  formation  of  emholi. 

The  other  changes  of  the  liver  consisted  in  intiltration  of  round  granulation  cells 
aroTind  the  portal  vessels.  The  fatty  degeneration  and  the  necrosis  was  much  less 
marked  in  this  place;  e^en  in  the  most  advanced  cases  a  certain  numhcr  of  normal 
liver  cells  were  .always  found  here.  Some  of  the  liver  cells,  particularly  around  the 
portal  spaces  and  adjoining  the  portions  most  degeneraled,  contained  several  nuclei, 
generally  oval,  and  loss  vesicular  in  appearance  than  the  normal  nucleus.  Rows  of 
smaller  cells  with  similar  nuclei  were  also  found,  and  appeared  to  indicate  an  attempt 
at  regeneration.  A  few  of  the  specimens  from  autopsies  very  shortly  after  death  and 
which  were  at  once  placed  in  alcohol  showed  rather  ill-defined  nuclear  figures. 

In  the  kidneys  the  changes  were  generally  those  indicating  an  intense  parenchy- 
matous degeneration.  They  were  most  marked  in  the  tubules  of  the  labyrinth.  The 
glomeruli  in  the  most  cases  were  atfected.  The  capsular  space  was  dilated  and  filled 
with  a  granular  exudation  coagulated  hy  the  alcohol,  and  frequently  in  this,  round 
hyaline  masses  were  found.  The  epithelial  cells  of  the  convoluted  tubules  were  very 
much  swollen  and  the  tubules  often  dilated.  The  cells  often  contained  larger  and 
smaller  fat  drops  shown  by  the  clear  sjiaces  remaining  after  this  was  dissolved  out  by 
the  alcohol,  but  the  principal  change  was  a  hyaline  degeneration  of  the  cells.  The 
cells  contained  an  immense  number  of  clear  hyaline  granules  which  stained  more 
brightly  with  eosin.  In  many  cases  there  appeared  to  be  a  well-defined  margin  to  the 
cells,  and  over  this  what  appeared  to  be  a  row  of  cilia.  Examination  with  high- 
power  objectives  showed  this  to  be  composed  of  oblong  granules  of  the  same  hyaline 
material  as  that  within  the  cells,  and  apparently  represented  an  exudation.  In  the 
dilated  tubules  there  were  large  and  smaller,  generally  round,  masses  of  similar  hya- 
line material. 

The  most  peculiar  change  in  the  kidneys  in  some  cases  was  the  presence  of  masses 
of  colloid  material  aud  crystals  in  the  tubules.  This  colloid  material  was  found  iu 
the  loops  of  Henle  and  in  the  collecting  tubules.  It  was  sometimes  in  the  form  of 
round  masses  and  sometimes  in  irregular  clumps,  apparently  formed  from  aggrega- 
tion of  the  round  masses.  These  were  sometimes  united  to  each  other  to  form  long 
chains.  When  these  bodies  are  seen  singly  the  center  appears  depressed  and  some- 
times stained  more  deeply  than  the  periphery.  They  stained  with  nearly  all  of  the 
nuclear  stains,  but  particularly  with  Bismarck  brown  and  hfematoxylin.  They  were 
highly  refractive,  and  either  perfectly  hy.aline  or  composed  of  numerous  laminoe, 
like  starch  granules.  They  were  generally  found  iu  the  lumen  of  the  tubules,  but 
in  one  case  there  was  a  large  aggregation  between  the  epithelium  and  the  wall  of 
the  tube.  The  crystalline  masses  were  found  in  every  case  examined,  aud  differed  in 
all  respects  from  the  material  just  described.  They  were  of  a  yellowish  or  yellowish- 
green  color,  with  sharp  edges,  very  highly  refractive,  and  with  numerous  radiating 
lines  and  fractures  running  from  the  periphery  to  the  center.  They  did  not  stain 
with  any  of  the  reagents  used.  In  addition  to  these  bodies,  in  some  cases  the  tubules 
contained  beaded  strings  of  a  substance  evidently  derived  from  the  blood,  and  which 
stained  intensely  with  both  eosin  and  picric  acid.  Cnstsboth  epithelial  and  hyaline 
were  found,  the  latter  apparently  composed  of  aggregations  of  the  same  hyaline 
material  which  was  fouud  in  the  epithelium.  In  some  of  the  tubules  considerable 
numbers  of  leucocytes  were  found,  but  in  general  it  was  remarkable,  in  view  of  the 
extent  of  the  parenchymatous  degeneration,  how  little  cellular  infiltration  f  hei-e  was. 

The  changes  in  both  the  liver  and  kidney  appear  to  be  due  to  a  general  toxemia 
rather  than  to  the  local  presence  of  infectious  agents.  They  are  diffuse,  affecting 
the  whole  of  the  organs,  aud  not  small  areas. 


154  ETIOLOGY   AND   PREVENTION    OP    YELLOW    FEVER. 


5^. 


■)  O  c^  °' 


•LC\   /^ 


Fig.  10. — Section  of  liver  but  little  affected,    a,  necrotic  ma.sse.g.     X  150. 


ETIOLOGY    AND    PEEVENTION    OF   YELLOW   FEVER.  155 


Coit> 


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Figs.  11  and  12.— 'From  same  liver,    a,  necrotic  mas.ses ;  «,  small  necroses  in  liver  cells,  not  .so  sharply 
differentiated  as  the  larger  masses,    b,  leucocj-tes;  c,  liver  cell,  in  hegiuuin^  necrosis.     X  400. 


156  ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER. 


\:"\- 


Fig.  13.— From  a  liver  in  an  advanced  stajie  of  degeneration.     The  .spaces  between  capillavies  occu- 
pied by  the  necrotic  mas-ses;  fat  and  debris  of  liver  cells  witli  a  few  leacocytes.     X  300. 


Fir.  14- — From  same  liver:  necrotic  masses  witli  lii-jlier  power,  Leitz  one-twelfth  immer.sion.    In  one 
of  the  bodies  a,  a  vacuole,  inclosing  a  small  body. 


ETIOLOGY   AND    PREVENTION    OF    YELLOW   FEVER, 


157 


^3 


Fig.  15. — Liver  cells,  with  necrotic  masses, 
and  small  masses  between  and  in  the  liver 
cells. 


Fig.  16.— Necrotic  mass  in  fatty,  degen- 
erated liver  cells. 


Fig.  17. — Glomerulus  with  granular  and  hyaline  material  in  capsular  space.      Fig.  18. — Section  of  kidney,  with  hyaline 

degeneration  of  epithelium  and  hyaline 
and  granular  material  in  the  lumen  of 
tubuiea. 


158 


ETIOLOGY    AND    PKEVENTION    OF    YELLOW    FEVER. 


I^enoratiou  of  epithelium  ;  Muller's  fluid  specime^^ 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVJ£E,  159 


;:a'-^ 


Tig.  20.— Tubules  containing  colloid  material  and  crystals. 


uMi. 


VII-DESCRIPTIOX  OF  MICROORGANISMS  WHICH  HAVE  BEEN 
CLAIMED  TO  BE  THE  CAUSE  OF  YELLOW  FEVER. 

THE   CEYPTOCOCOUS  XANTHOGENICUS   OF   DR.  DOMINGOS  FEEIEE,  OF 

BRAZIL. 

In  his  priucipal  work,  "Doctrine  Microbienne  de  la  fievre  Janne,"  pub- 
lished in  1885,  Dr.  Domingos  Freire  gives  the  following  account  of  his 
''Cryptococcus  Xauthogeuicus": 

Wheu  we  follow,  with  all  the  care  and  attention  possible,  the  march  of  the  clevelop- 
meut  which  characterizes  the  germs  which  produce  yellow  fever,  we  acquire  the 
certainty  that,  commencing  to  present  themselves  under  the  form  of  little  points 
almost  imperceptible,  they  afterwards  gradually  increase  in  diameter  until  they  attain 
considerable  dimensions,  so  that  these  little  beings,  which  at  the  outset  had  the 
aspect  of  very  little  grains  of  sand,  not  measuring  more  than  0.001  to  0.002  millimetre 
in  diameter,  arrive,  little  by  little,  to  such  a  development  that  th<y  reach  the  dimen- 
sionsof  0.005, 0.007,  or  0.008  millimetre,  and  sometimes  even  more  in  certain  determined 
conditions. 

"When  they  have  attained  the  adult  age  these  cells  are  broken  at  diverse  points  and 
discharge  their  contents,  composed  of  spores  already  formed,  mixed  with  a  viscous 
substance  of  a  yellow  color,  composedof  pigmentary  and  protoplasmic  substance,  and 
of  the  liquids  elaborated  by  the  cells.     *     *     * 

The  microbe  xantnogenicus  is  a  co.smopolitau ;  it  does  not  select  its  domicile  in  any 
organ  and  has  no  preference  for  any  organic  liqnid.  We  have  encounlered  it  with 
the  same  characters,  the  same  opulence  of  proliferation  in  the  brain,  in  the  muscles, 
in  the  liver,  in  the  spleen,  in  the  kidneys,  in  the  lungs,  in  the  blood,  in  the  urine,  in 
the  bile,  in  the  vomit,  and  even  in.  the  cephalo-rachidian  fluid.  However,  it  is  neces- 
sary to  establish  a  well-drawn  distinction  as  to  the  blood.  The  blood  of  the  general 
circulation  shows  itself  much  less  charged  with  the  microbes  than  the  blood  of  the 
capillaries.  Thus,  if  I  could  admit  any  preference  on  the  part  of  the  microbe  xantho- 
geuicu.s,  I  would  say  that  it  pleases  itself  better  in  the  blood  of  the  capillaries,  in  the 
blood  which  bathes  immediately  the  anatomical  elements.     *■     *     * 

The  occasion  seems  to  us  a  favorable  one  in  order  to  call  attention  to  some  indis- 
pensable precautions  when  the  microbes  of  yellow  fever  are  to  be  sought  in  organic 
solids  and  liquids.  While  it  is  extremely  easy  to  perceive  the  presence  of  the  microbes 
of  yellow  fever  in  the  urine  and  bile,  for  example,  by  placing  a  drop  of  these  liquids 
upon  a  glass  slide,  covering  it  with  a  thin  glass  cover,  and  examining  it  with  a  power 
of  450  to  740,  or  780  diameters,  this  proceeding  can  not  be  employed  when  the  blood 
is  to  be  examined.  If  we  proceed  in  this  manner  the  globules  wiU  hide  nearly  all  the 
microbes  and  the  observer  will  wrongly  conclndc  that  they  are  very  rare  in  this 
organic  liquid.  Not  only  does  the  form  of  the  microbe  offer  a  certain  resemblance  to 
that  of  the  red  coriiuscles,  but  these  latter  in  adhering  together  enveloii  the  micro- 
biau  cells,  and,  on  the  other  hand,  cast  upon  the  cells  a  jet  of  light,  which  makes 
them  disappear  from  the  field  of  the  raicoscope.  But  if  we  dilute  a  little  drop  of 
blood  in  a  pure  solution  of  sulphate  of  soda  and  place  it  under  the  objective,  the 
microbes  bacome  visible  and  will  appear  in  considerable  quantity. 
160 


ETIOLOGY   AND    PREVENTION    OF    YELLOW   FEVER.  161 

It  is  likewise  necessary  to  make  a  preparation  previously  for  the  examination  of 
the  cerebi'al  mass  and  of  the  muscles.  They  should  be  triturated  in  a  sterilized  mortar 
and  mixed  afterward  with  distilled  water  entirely  deprived  of  organisms,  filtered 
through  fine  linen  which  has  been  passed  rapidly  through  the  flame  of  an  alcohol 
lamp,  and  afterwards  a  drop  of  the  filtered  liquid  should  be  placed  upon  a  glass  slide. 
If  we  withdraw  a  little  piece  of  brain  or  of  muscular  fiber,  even  triturated,  we  will 
not  perceive  anything  abnormal  under  the  microscope  unless  it  be  the  anatomical 
elements  more  or  less  deformed  by  trituration. 

It  is  not  the  same  for  the  liver.  It  suffices  to  withdraw  a  hit  of  this  organ  and  to 
crush  it  between  two  glass  slides;  upon  observing  it  under  the  microscope  we  per- 
ceive at  once  a  multitude  of  microbes.  This  is  because  in  the  muscles  the  microbes 
are  lodged  between  the  fibrillse  and  in  the  substance  which  surrounds  them,  and  in 
the  brain  they  are  found  in  the  interior  of  the  nerve-cells,  which  must  first  be  de- 
stroyed by  trituration  in  order  that  their  parasitic  hosts  may  become  visible. 

I  would  say  in  the  first  place  that  the  description  above  given  of  the 
cryptococcus  santhogenicus  does  not  correspond  with  the  characters 
of  the  microorganism  which  Dr.  Freire  presented  to  me  as  his  yellow 
fever  germ ;  and,  secondly,  that  no  such  organism  as  he  has  described 
or  as  was  present  in  the  cultures  which  he  gave  me,  is  to  be  found  in 
the  blood  or  tissues  of  yellow-fever  patients. 

The  only  explanation  of  the  remarkable  versatility  as  to  the  form 
which  Dr.  Freire  has  ascribed  to  his  "cryptococcus"  on  different  pages 
of  the  work  referred  to,  which  I  can  conceive  of  is  that  offered  by  Dr. 
Araujo  Goes,  one  of  his  medical  confreres  and  critics  in  Eio  de  Janeiro, 
viz,  that  Dr.  Freire  has  mistaken  deformed  blood  corpuscles,  fat  glo- 
bules from  the  liver,  and  the  debris  of  tissue  elements  in  his  trituration 
of  muscle,  brain,  etc.,  for  microorganisms.  Dr.  Freire  frequently  speaks 
of  his  cryptococcus  as  being  endowed  with  active  movement.  It  is  well 
known  to  microscopists  that  minute  particles,  organic  or  inorganic,  when 
suspended  in  a  fluid,  undergo,  under  certain  circumstances,  a  rapid 
vibratory  motion,  known  as  the  brownian  or  molecular  movement.  The 
microorganism,  a  micrococcus,  which  Dr.  Freire  presented  to  me  as  his 
yellow-fever  germ,  like  other  similar  organisms,  presents  these  molecu- 
lar movements  when  suspended  in  a  fluid,  but  it  has  no  proper  vital 
movements,  such  as  are  manifested  by  many  of  the  bacilli.  The  fat 
drops  from  crushed  liver  tissue,  or  the  debris  of  muscle  fibrillse,  present 
these  molecular  movements,  and  in  form  and  appearance  present  some 
resemblance  to  micrococci.  They  are  easily  distinguished,  however,  by 
chemical  tests  and  staining  agents,  I  may  remark  here  that  prior  to 
his  visit  to  Paris  in  1887,  Dr.  Freire  seems  not  to  have  made  use  of  the 
method  of  staining  with  aniline  dyes.  In  an  address,  made  while  in 
Paris,  he  defends  himself  from  the  charge  which  some  one  seems  to 
have  made,  that  he  had  neglected  this  means  of  recognizing  microor- 
ganisms, in  the  following  language  : 

We  know  that  in  order  to  color  a  microbe  it  is  necessary,  first,  to  kill  it  and  then 
to  wash  the  little  microscopic  cadaver  by  means  of  reagents  possessing  the  power  of 
dissolving  all  matters  foreign  to  its  skeleton.  At  the  outset  I  applied  myself  to  the 
study  of  the  yellow-fever  microbe  in  a  fresh  state.     I  fed  it  with  the  best  food,  lea 

4067 11 


162     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

■meiUeurs  engrais,  for  the  purpose  of  witnessing  the  difTerent  phases  of  its  evolution 
from  its  birth  to  its  death. 

Nevertheless,  in  fault  of  other  accusations,  some  authors  have  reproached  me  with 
not  having  colored  my  microbe.  Alas,  what  a  miserable  objection!  Is  it  necessary 
in  order  to  affirm  the  existence  of  a  microbe,  which  swarms  by  millions  in  the  urine, 
in  the  bile,  in  the  blood,  in  the  tissue,  etc. ;  is  it  necessary  to  mask  them,  to  disguise 
them  under  a  costume  of  carnival,  in  order  to  please  certain  microscopists  ?  M.  Pas- 
teur has  never  colored  his  microbes ;  and,  nevertheless,  everyone  admits  the  exist- 
ence of  the  bacillus  of  charbon,  of  the  corpuscles  of  p^brine,  of  the  micrococcus  of 
fowl  cholera,  etc. 

»  *  *  Do  not  think,  gentlemen,  that  I  fear  the  application  of  coloring  j)rocesses 
to  the  search  for  the  microbe  of  yellow  fever.  Far  from  it.  In  order  to  show  you 
that  the  criticism  which  I  have  just  made  is  not  due  to  prejudice,  I  will  say  to  you 
that  such  processes  have  recently  been  employed  upon  the  yellow-fever  microbe  with 
complete  success. 

The  method  of  cultiyating  in  solid  media  and  of  isolating  micro- 
organisms by  means  of  plate  cultures  orEsmarch  tubes,  seems  also  to 
have  been  unknown  to  Freire  prior  to  his  visit  to  Paris.  All  of  the 
cultures  left  in  his  laboratory  at  the  time  of  my  arrival  were  in  liquid 
media  and  preserved  in  Pasteur  flasks.  He  brought  from  Paris,  how- 
ever, a  number  of  cultures  in  agar-agar,  and  among  them  one  which  he 
presented  to  me  as  a  pure  culture  of  his  yellow  fever  microbe.  This 
was  a  micrococcus,  which  multiplies,  as  do  other  microorganisms  of  the 
same  class,  by  binary  division  and  not  by  the  growth  of  the  separate 
cells  to  comparatively  large  dimensions,  and  the  formation  of  endoge- 
nious  spores,  which  are  released  by  rupture  of  the  cell  wall  of  the  mother 
cell,  as  described  by  Dr.  Freire.  This  mode  of  multiplication  is  not 
known  among  the  bacteria,  and  does  not  occur  in  the  micrococcus 
which  Dr.  Freire  placed  in  my  hands  as  his  yellow  fever  microbe,  and 
which  I  have  had  in  cultivation  continuously  since  my  visit  to  Brazil  in 
1887.  This  is  a  simple  staphylococcus  which  multiplies  by  binary  divi- 
sion, and  upon  the  surface  of  nutrient  agar  forms  a  milk-white  mass. 
I  have  never  seen  it  produce  either  the  yellow  or  the  black  pigment 
which  Dr.  Freire  ascribes  to  it.  In  an  address  made  by  him  in  Paris, 
in  April,  1887,  he  repeats  the-statement  previously  made  in  his  princi- 
pal work,  in  the  following  language : 

Each  adult  cell  is  ruptured  in  one  or  several  points  and  allows  to  escape  its  con- 
tents composed  of  grrms  which  are  to  perpetuate  the  species,  and  two  pigments,  one 
yellow,  destined  to  iniiltrate  the  tissues  and  produce  the  icteric  color  which  has 
"■iven  name  to  the  malady,  the  other  black,  insoluble,  and  destined  to  be  carried  along 
by  the  circulatory  current,  producing  either  capillary  obstructions  or  blood  stasis  in 
the  parenchyma  of  the  organs. 

This  account  is  entirely  fanciful.  Kot  only  does  Dr.  Freire's  micro- 
coccus not  produce  such  jjigment  as  he  describes,  but  i-n  yellow  fever  no 
black  pigment  granules  are  found  in  the  capillaries  or  the  parenchyma 
of  the  organs,  as  is  the  case  in  malarial  fevers.  Moreover  the  pigment 
which  gives  a  black  color  to  the  vomited  matters,  and  to  the  contents 
of  the  intestine  in  most  fatal  cases,  is  fully  accounted  for  and  does  not 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER.  163 

result  from  the  presence  of  Dr.  Freire's  crpy  tococcus  or  of  any  otlier 
microorganism.  It  is  blood  pigment  changed  by  the  acid  secretions  of 
the  stomach  and  present  in  that  viscus  as  a  result  of  passive  hemorrhage 
from  the  mucous  membrane.  This  I  have  verified  very  many  times  by 
microscopical  examinations  which  have  shown  the  granular  brown  pig- 
ment, which  gives  color  to  the  "  black  vomit,"  to  be  closely  associated 
with  little  masses  of  decolorized  blood  corpuscles ;  and  it  has  been 
demonstrated  by  a  spectroscopic  examination  made  at  my  request  by 
Dr.  George  Kemp,  of  the  Hoagiand  laboratory.  Dr.  Freire's  micrococ- 
cus liquefies  gelatine  quite  slowly,  forming  a  cup  shaped  cavity,  at  the 
bottom  of  which  the  cocci  accumulate,  forming  a  white  deposit,  as  shown 
in  Fig.  5,  PI.  in.  The  morphology  is  shown  by  my  photomicrograph 
from  a  preparation  stained  with  fuchsin,  Fig.  1,  PI.  in. 

That  this  micrococcus  bears  no  relation  to  the  etiology  of  yellow 
fever  is  fully  proved  by  my  extended  culture  experiments  in  Havana 
during  the  summers  of  1888  and  1889.  In  the  entire  series  of  autopsies 
I  have  made  cultures  from  the  liver,  and  in  a  considerable  number  from 
blood  obtained  directly  from  the  heart,  and  I  have  not  obtained  this 
micrococcus  of  Freire  in  a  single  instance,  although  the  culture  medium 
commonly  employed — flesh  peptone-gelatine — is  a  very  favorable  one 
for  the  growth  of  this  coccus.  Nor  has  it  been  found  in  the  extended 
series  of  sections  which  I  have  made  from  the  liver  and  kidney  pre- 
served in  alcohol  from  my  Havana  autopsies.  In  one  case  only  (case 
10,  1888)  I  have  found  micrococci  in  sections  from  the  kidney,  but  as 
the  micrococcus  of  Freire,  in  its  form  and  dimensions,  resembles  many 
others,  it  is  impossible  to  say  that  this  is  or  is  not  the  Freire  coccus. 
The  finding  of  micrococci  in  this  case,  however,  does  not  invalidate  the 
general  result,  which  is  that  micrococci  are  not  found  in  the  Mood  and 
tissues  of  yellow  fever  cadavers. 

The  micrococcus  of  Freire  is  killed  by  10  minutes'  exposure  to  a 
temperature  of  60°  C.  (140°  F.);  Its  vitality  is  not  destroyed  by  a  freez- 
ing temperature.  I  have  subjected  it  for  an  hour  and  a  half  to  a  tem- 
perature of  15°  C.  below  zero  (5°  F.)  in  a  freezing  mixture  of  salt  and 
ice,  and  found  that  it  grew  as  usual  when  planted  in  flesh-peptone-gela- 
tine,  and  kept  at  a  temperature  of  26°  C.  A  stick  culture  in  the  same 
medium,  placed  in  an  exposed  attic  in  the  laboratory  in  Baltimore,  from 
January  17  to  29,  at  a  temperature  ranging  from  2°  to  10°  C,  not  only 
was  not  killed,  but  showed  decided  growth.  In  short  it  is  a  hardy 
micrococcus,  which  grows  at  comparatively  low  temperatures  and  pre- 
serves its  vitality  in  sealed  tubes  for  several  months. 

THE  YELLOW-FEVER  "GERM"  OF  DR.  CARMONA  Y  VALLE,  OF  MEXICO. 

Dr.  Manuel  Carmona  y  Valle  has  given  an  account  of  his  researches 
and  supposed  discovery  in  his  memoir,  entitled,  "LeQons  sur  I'etiologie 
et  la  prophylaxie  de  la  flevre  jaune,"  Mexico,  1885. 


164     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

I  am  indebted  to  Dr.  Carmona  for  a  copy  of  this  work,  which  he  pre- 
sented to  me  at  the  time  of  my  visit  to  Mexico.  The  following  inscrip- 
tion, signed  by  him,  is  upon  the  title-page,  and  is  a  frank  acknowledg- 
ment that  the  author  Las  modified  bis  views  very  considerably  with 
reference  to  his  earlier  observations  : 

A.  M.  le  Dr.  Sternberg  : 

Quoiqu'il  soit  n^cessaire  de  modifier  toute  la  partie  relative  h  la  movphologie  et 
aux  cnltures  du  microganisme. 

Mexico,  le  26  Septenibre,  1887. 

Dr.  Carmona  y  Valle. 

At  the  time  of  my  visit  to  his  laboratory  (September,  1887)  Dr.  Car- 
mona was  inclined  to  attach  some  importance  to  a  bacillus  which  he 
had  obtained  in  his  cultures  from  yellow-fever  urine  sent  to  him  from 
Vera  Cruz.  This  bacillus  is  shown  in  my  photomicrograph,  Fig.  4,  1*1. 
Ill,  which  is  from  a  slide  mounted  by  Dr.  Angel  Gaviiio  Yglesias  in 
Dr.  Carmona's  laboratory.  Associated  with  the  large  bacillus,  shown 
in  the  photomicrograph,  there  is  another  slender  bacillus  in  smaller 
numbers,  which  is  seen  upon  looking  over  the  slide.  This  large  bacil- 
lus was  also  present  in  a  culture  from  yellow-fever  urine  which  Dr. 
Carmona  presented  to  me,  and  which,  by  the  use  of  Esmarch  roll  tubes, 
I  found  to  contain  several  other  bacilli  and  a  micrococcus.  The  large 
bacillus  is  of  the  "subtilis"  group.  It  liquefies  gelatine  quite  rapidly, 
and  forms  large  oval  spores. 

Not  having  obtained  it  in  my  cultures  from  the  blood  and  tissues  oi 
yellow-fever  cadavers,  or  from  urine  drawn  through  the  walls  of  the 
bladder  in  a  considerable  number  of  cases,  I  must  regard  its  presence 
in  Dr.  Carmona's  cultures  from  urine  collected  for  him  in  Yera  Cruz 
as  entirely  accidental,  and  without  significance  so  far  as  the  etiology  of 
yellow  fever  is  concerned. 

THE  YELLOW-FEVER   GERM  OF  DR.   CARLOS  FINLAY,   OF  HAVANA. 

(Mid'ocoocus  ietragenus  versatilis,  Sternberg.) 

Dr.  Carlos  Finlay  having,  in  his  earlier  researches,  observed  micro- 
cocci in  groups  of  four  in  cultures  obtained  from  mosquitoes  which  he 
had  allowed  to  fill  with  blood  from  yellow  fever  patients,  inferred  that 
the  micrococci  came  from  the  blood  of  the  sick,  and  that  the  grouping 
in  fours  was  a  character  by  which  he  could  distinguish  this  micro- 
organism, which  he  named  Micrococcus  tetragenus  fehris  Jiavce,  upon 
the  supposition  that  it  was  concerned  in  the  etiology  of  yellow  fever. 

During  the  winter  of  1887-'88  Dr.  Finlay  sent  me  a  number  of  his 
"mosquito  cultures,"  which  I  found  to  contain  a  variety  of  micro- 
organisms. Among  these  a  large  micrococcus  grouped  in  tetrads  was 
most  conspicuous.  This  I  isolated  and  studied  in  pure  cultures,  and 
have  since  named  Micrococcus  tetragenus  versatilis,  a  name  which  Dr. 
Finlay  has  accepted. 


ETIOLOGY   AND    PREVENTION    OF   YELLOW   FEVER.  165 

The  characteristic  mode  of  grouping  is  shown  in  Fig.  3,  PI.  III.  Some 
bacteriologists  would  perhaps  be  disposed  to  place  it  among  the  Sarcintei 
but  I  have  never  observed  any  evidence  of  division  in  a  third  plane, 
forming  packets  of  eight  or  more  elements,  such  as  are  characteristic 
of  this  genus.  I  have  called  it  "  versatilis  "  because  it  is  very  versatile 
both  in  the  grouping  of  the  elements  and  in  their  dimensions.  In  the 
same  culture  very  wide  differences  in  size  are  observed,  and  at  different 
times  and  in  different  media  these  variations  are  very  noticeable.  The 
grouping  also  varies  greatly;  sometimes  the  greater  number  of  the 
elements  are  arranged  in  tetrads,  or  in  pairs  in  which  the  large  oval 
elements  are  upon  the  point  of  dividing  transversely  to  the  line  by  which 
the  binary  division  of  a  single  element  is  marked.  But  often  there  are 
irregular  groups  of  three  or  more  elements,  or  there  may  be  a  chain 
of  tetrads  which  remain  attached  one  to  the  other. 

In  agar-stick-cultures  a  rather  thick  and  viscid  yellow  mass  is  formed 
on  the  surface,  about  the  point  of  puncture ;  and  in  the  course  of  a  week 
or  ten  days,  at  a  temperature  of  20°  to  25°  C,  this  extends  over  the  en- 
tire surface.  The  color  varies  from  cream  yellow  to  lemon  yellow.  The 
growth  upon  jDotato  is  similar  to  that  upon  agar.  In  stick  cultures  in 
flesh-peptone-gelatin  the  gelatin  is  liquefied  rather  slowly  near  the 
surface,  forming  a  deep  cup-shaped  cavity,  as  shown  in  Fig.  7,  PI.  III. 
Colonies  in  gelatin  roll-tubes  are  at  first  pale  yellow  and  later  lemon 
yellow  in  color;  they  are  opaque  and  spherical,  and  do  not  usually  cause 
liquefaction  of  the  gelatin  for  several  days.  The  microorganism  has  no 
proper  movements  and  is  aerobic,  no  growth  occurring  in  an  atmos- 
phere of  hydrogen.    It  is  not  pathogenic  for  rabbits  or  guinea  pigs. 

I  have  occasionally  obtained  a  few  colonies  of  this  micrococcus  in  my 
cultures  from  the  contents  of  the  stomach  and  intestine  of  yellow-fever 
cadavers,  and  in  one  case  (case  8, 1888)  I  obtained  it  from  the  liver  kept 
in  an  antiseptic  wrapping  for  48  hours.  In  this  case  it  was  associated 
with  staphylococcus  pyogenes  aureus.  There  is  no  reason  to  believe  that 
it  has  anything  to  do  with  the  etiology  of  yellow  fever.  My  researches 
show  that  it  is  a  very  common  organism  upon  the  surface  of  the  body 
of  i)atients  in  the  hospitals  of  Vera  Craz  and  of  Havana,  and  quite  as 
common  in  cases  not  having  yellow  fever  as  in  those  sick  with  this  dis- 
ease. In  Brazil,  in  1887,  my  friend  Dr.  Goes  obtained  it  in  a  culture 
from  blood  drawn  from  the  finger  of  a  yellow-fever  case  in  the  small- 
pox hospital.  My  inference  then  was  that  its  presence  was  accidental, 
and  due  to  contamination  of  the  drop  of  blood  while  collecting  it ;  and 
I  believe  this  to  have  been  the  case  when  it  has  been  present  in  Dr. 
Finlay's  cultures  from  blister  sernm.  In  a  case  of  brain  disease,  and  in 
a  case  of  skin  disease,  in  which  Drs.  Finlay  and  Delgado  applied  blisters 
and  collected  serum  by  their  usual  method,  I  obtained  this  micrococcus 
in  Esmarch  roll-tubes  to  which  this  serum  had  been  added.  These 
cases  had  not  been  associated  in  any  way  with  yellow-fever  patients, 


166  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

and  the  blister  serum  was  collected  at  my  suggestion  as  a  control  ex' 
perimeut,  inasmuch  as  Drs,  Finlay  and  Delgado  had  obtained  this  micro- 
coccus in  their  "mosquito  cultures,"  and  in  blister  serum  from  yellow- 
fever  cases.  Its  absence  in  cultures  from  the  blood  in  a  large  series  of 
cases  fully  supports  the  inference  that  its  occasional  presence  in  blood 
drawn  from  the  finger,  or  in  blister  serum,  is  due  to  accidental  contami- 
nation from  the  surface  of  the  body  or  from  the  atmosphere. 

Dr.  Finlay  himself,  when  I  left  Havana  last  year,  had  about  given  up 
the  idea  that  this  tetragenus  is  the  cause  of  yellow  fever.  This  is  shown 
by  the  following  letter  from  him: 

Havana,  August  29,  1889. 
My  Dear  Doctor:  I  send  you  a  copy  of  the  r^snm^  of  our  investigations  during 
fhe  year,  May,  1888-89,  whicli  Dr.  Delgado  and  myself  presented  at  tlie  beginning 
of  the  year.  You  will  see  that  vre  did  not  claim  to  have  demonstrated  that  our  "  tetra- 
genus "  was  the  actual  germ  of  yellow  fever,  but  merely  that  in  our  recent  investiga- 
tions, carried  out  with  methods  which  we  deemed  to  be  reliable,  we  had  again  found 
the  same  microorganism  in  yellow  fever  finger  blood  and  in  blister  serum,  and  also 
in  cadaveric  products  of  two  yellow  fever  autopsies.  "We  likewise  expressed  the  hope 
that  you  would  undertake  comparative  experiments  in  order  to  determine,  first, 
whether  it  was  a  fact  that  by  the  culture  methods  which  we  had  described  our 
tetragenus  could  be  demonstrated  in  most  of  the  products  collected  during  life  from 
yellow  fever  patients,  and,  second,  whether  that  microorganism  is  exclusively  found 
in  such  patients.  I  am  aware  that  the  results  of  three  samples  of  yellow  fever  blis- 
ter serum  and  seven  samples  of  blister  serum  from  acclimated  subjects  have  given  a 
negative  answer  on  the  second  point.  Y''et  lean  not  wholly  divest  myself  of  the  sus- 
picion that  the  greater  frequency  with  which  we  have  found  the  tetragenus  in  onr 
yellow  fever  cultures  (from  material  collected  during  life)  may  have  some  signifi- 
cance, even  admitting,  as  I  do,  that  before  any  etiological  importance  can  be  claimed 
for  it  quite  a  number  of  serious  objections  would  have  to  be  encountered  besides 
showing  that  it  is  not  to  be  found  in  localities  where  yellow  fever  is  unknown. 
I  am,  my  dear  doctor,  yours,  very  faithfully, 

Carlos  Finlay. 
Dr.  G.  M.  Sternberg,  U.  S.  Army, 

Havana. 

Finally,  I  may  say  that  this  "tetragenus"  is  comparatively  large,  and 
conspicuous  by  reason  of  its  grouping  in  tetrads,  and  that  it  is  promptly 
stained  by  the  aniline  colors.  It  should  therefore  be  found  in  my  sec- 
tions of  the  various  organs  if  present  in  the  blood  of  yellow  fever 
patients.  It  has  not  been  found  in  the  numerous  sections  made  from 
forty  cases  in  which  I  have  made  autopsies  in  Havana,  unless  possibly 
the  cocci  found  in  a  single  case  in  sections  from  the  kidney  (case  10, 
188S)  are  identical  with  Dr.  Finlay's  tetragenus.  As  remarked  in  the 
account  of  Dr.  Freire's  coccus,  such  identity  can  not  be  established  by 
microscopic  examination  alone,  and  the  question,  which  is  of  little  im- 
portance in  view  of  the  facts  stated,  must  remain  unanswered. 

But  one  thing  is  very  evident,  and  that  is  that  the  researches  of  Dr. 
Finlay  give  no  support  to  the  claims  of  Freire,  inasmuch  as  the  micro- 
coccus which  has  especialiy  engaged  his  attention  is  entirely  different 
from  that  of  the  Brazilian  investigator. 


ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVEE.     167 

THE  BACILLUS  OF  DR.  PAUL  GIBIER. 

(Bacillus  iej)i7ia  lethalis,  Sternberg.) 

t)r.  Paul  Gibier,  a  Freucli  bacteriologist,  went  to  Cuba  in  the  autumn  of 
1887  in  the  expectation  of  finding  the  yellow  fever  microbe  of  Dr.  Freire, 
who  had  spent  some  time  in  his  laboratory  in  Paris.  This  is  shown,  as 
well  as  his  failure  to  realize  this  expectation,  in  the  following  communi- 
cation made  by  him  to  the  French  Academy  of  Sciences: 

Havana,  Jamiary  22,  1888. 

At  tlie  commencement  of  tbe  year  1887  Dr.  Domingos  Freire,  professor  in  the  fac- 
ulty of  medicine  of  Rio  de  Janeiro,  came  to  Paris  in  order  to  present  to  the  scientific 
pnblic  his  studies  upon  yellow  fever.  M.  Freire  was  presented  to  me  by  Dr.  Rebour- 
geou,  who  had  studied  this  malady  with  him  in  Bradl,  The  laboratory  of  compara- 
tive pathology  of  the  museum  was  opened  to  these  savants,  who  resumed  the  experi- 
ments, the  results  of  which  had  previously  been  published  by  M.  Freire.  I  was  re- 
quested by  Dr.  Freire  to  examine  the  cultures  which  he  had  brought  with  him,  and 
to  treat  them  by  the  new  bacteriological  methods,  which  had  not  yet  been  applied  in 
his  researches.  After  these  investigations,  made  in  common,  M.  Freire  had  the  kind- 
ness to  associate  me  in  a  communication  made  in  his  own  name  and  that  of  Rebour- 
geon  to  the  Academy  of  Sciences  during  the  month  of  March,  1887. 

Since,  and  as  a  result  of  this  communication,  I  received  from  the  minister  of  public 
instruction  the  mission  to  go  and  "study  yellow  fever  in  the  countries  where  it  pre- 
vails habitually,  and  the  prophylactic  measures  which  may  be  opposed  to  this  malady.*' 

Dr.  Gibier  arrived  in  Havana  in  JS"ovember,  1887,  and  proceeded  to 
inake  bacteriological  researches  by  approved  methods,  the  results  of 
which  he  announces  as  follows  in  the  communication  from  which  we 
have  quoted : 

Results  obtained. — I  am  obliged  to  confess  here,  however  much  it  may  cost  me, 
that  my  results  contradict  in  an  absolute  manner  the  facts  advanced  by  M.  Domin- 
gos Freire,  from  whom  I  have  the  regret,  as  well  as  the  duty,  to  separate  myself. 

The  Mood. — In  a  great  number  of  preparations,  fresh  or  colored,  it  has  been  impos- 
sible for  me  to  verify  the  presence  of  microorganisms.  The  cultures  repeated  a  great 
number  of  times  remained  sterile.     »     *     » 

The  numerous  sections  which  I  have  made  of  the  different  viscera  have  also  failed 
to  show  me  the  presence  of  microbesi 

Having  convinced  himself  that  neither  the  micrococcus  of  Freire,  nor 
anyothermicroorganism  was  presentin  the  blood  of  yellow  fever  patients, 
Dr.  Gibier  turned  his  attention  to  the  microorganisms  present  in  the 
alimentary  canal,  and  isolated  from  the  contents  of  the  intestine  of  one 
or  more  cases  a  liquefying  bacillus  to  which  he  was  inclined  to  attach 
especial  importance. 

Dr.  Gibier  kindly  placed  in  my  hands  a  culture  of  this  bacillus  upon 
my  arrival  in  Havana  in  the  spring  of  1888,  and  I  have  had  it  in  con- 
stant cultivation  since  that  time,  and  have  made  numerous  inoculations 
into  rabbits  and  guinea  pigs  which  show  that  it  is  pathogenic  for  these 
animals. 

But  my  extended  researches  give  no  support  to  the  supposition  that 
it  is  concerned  in  the  etiology  of  yellow  fever.    In  a  large  majority  of 


168     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

my  cases  it  lias  not  been  present  in  cultures  made  from  the  contents 
of  the  stomach  and  intestine  obtained  post-mortem,  or  from  the  alviue 
discharges  obtained  during  the  life  of  the  patient.  I  obtained  it  in 
comparatively  small  numbers  in  three  out  of  ten  cases  in  which  I  made 
autopsies  in  Havana  in  1888. 

Admitting  to  myself  the  possibility  that  the  specific  germ  of  the  dis- 
sease  might  be  absent,  or  only  occasionally  present,  in  the  contents  of 
the  intestine  obtained  post-mortem,  although  present  at  the  outset  of 
an  attack,  I  devoted  myself  especially  to  a  search  for  this  bacillus  in 
the  feces  of  yellow  fever  patients  during  my  stay  in  Decatur,  Ala- 
bama, in  the  autumn  of  1888.  The  result  of  this  research  was  to  show 
that  liquefying  bacilli  are  not  numerous  in  the  alviue  discharges  of  the 
sick,  and  that  the  bacillus  of  Gibier  was  only  present  in  a  limited  number  of 
cases  and  in  comparatively  small  numbers.  Another  liquefying  baccil- 
lus,  0,  was  found  more  frequently,  but  not  with  sufficient  constancy  to 
give  support  to  the  belief  that  it  bears  an  etiological  relation  to  the 
disease. 

Again,  in  my  extended  researches  in  Havana  during  the  summer  of 
1889  I  have  only  encountered  this  bacillus  in  my  cultures  from  the 
stomach  and  intestine  in  a  limited  number  of  cases. 

I  give  below  some  of  my  notes  with  reference  to  the  presence  of 
liquefying  bacilli : 

Autopsy  iS"o.  14  (No.  1  of  1889). — "B  coU  commnne  in  anaerobic  and  aerobic  culture 
from  stomach  and  intestine,  no  liquefying  colonies." 

Autopsy  No.  15. — "No  liquefying  colonies  in  cultures  from  intestine.  A  few  liquefy- 
ing colonies  in  Esmarcb  roll  tube  No.  1  from  stomach.  Liqueying  bacillus  with  large 
oval  end  spore  in  anaerobic  Esmarch  tube  from  intestine." 

Autopsy  No.  16. — "Liquefying  bacillus  (Bacillus  o  Decatur)  in  gelatine  Esmarch 
tubes  from  stomach  and  intestine." 

Autopsy  No.  17. — "  Cultures  from  intestine,  bacillus  a  and  a  single  liquefying  colony, 
not  Gibier's  bacillus." 

Autopsy  No.  18. — No  remarks  made  with  reference  to  liquefying  bacilli,  which  indi- 
cates their  absence. 

Autopsy  No.  19. — "No  liquefying  colonies  from  stomach  or  intestine  at  end  of  24 
hours." 

Autopsy  No.  20. — "  Bacillus  g,"  (Gibier's  bacillus).  "  Obtained  from  intestine.  Es- 
march roll  rubes  No.  1  and  No.  2  both  liquefied  at  end  of  24  hours." 

Autopsy  No.  21. — "  Gelatine  Esmarch  No.  1  from  intestine  liquefied  in  4d hours;  ba- 
cillus ee  "  (quite  different  fr-om  Gibier's). 

Autopsies  Nos.  22  and  23. — No  notes,  indicating  absence  of  liquefying  bacilli. 

Autopsy  No.  24. — "  Gelatine  Esmarch  roll  tube  No.  1  liquefied  in  24  hours ;  No.  2  on 
third  day  ;  bacillus  g." 

In  this  case  Gibier's  bacillus  was  present,  but  in  comparatiYely  small  numbers, 
because  Esmarch  tube  No.  3  of  the  series  did  not  contain  any  liquefying  colonies. 

Autopsy  No.  25. — "No  liquefaction  of  gelatine  Esmarch  tubes  from  intestine." 

Autopsy  No.  26. — "Doubtful  case,  diagnosis  not  supported  by  the  pathoJogical  ap- 
pearances ;  excluded." 

Autopsy  No.  27. — "Liquefying  bacillus  in  gelatine  Esmarch  tube  No.  1  from  intes- 
tine."   What  bacillus  was  not  determined. 

Autopsy  No.  28. — "No  liquefying  colonies  in  gelatine  Esmarch  tubes  from  intes- 
tine." 


ETIOLOGY   AND    PREVENTION   OF   YELLOW   FEVER.  169 

Autopsy  No.  29. — "  Gelatine  Esniarcli  tube  No.  1  liquefied  in  25  hours ;  single  colony 
in  No.  2;  No.  3  contains  nouliqnefying  colonies  only.  The  liquefying  bacillus  pre- 
sent is  bacillus  </."     (Gibier). 

Autopsy  No.  30. — "No  liquefaction  of  Esmarch  tubes  from  intestine  in  48  hours." 
Antopsy  No.  31. — "  No  liquefaction  of  gelatine  Esmarch  tubes  from  intestine  at  end 
of  48  hours." 

Autopsy  No.  32. — "No  liquefaction  of  Esmarch  tubes  from  intestine  in  48  hours." 
Autopsy  No.  33. — "  Esmarch  tube  No.  1  from  intestine  contains  liquefying  colonies 
at  end  of  48  hours;  bacillus  g ;  none  in  tubes Nos.  2  and  3,  which  contain  the  colon 
bacillus." 

These  notes  from  twenty  successive  cases  will  suffice  to  show  what 
has  already  been  stated,  viz:  that  this  bacillus  is  only  exceiDtionally 
present,  and  when  present  is  in  comparatively  small  numbers.  We  are 
therefore  obliged  to  exclude  it  from  consideration  from  an  etiological 
l)oint  of  view. 

I  may  here  say  that  in  my  cultures  made  directly  from  the  pure  cul- 
ture which  Dr.  Gibier  placed  in  my  hands,  and  from  the  intestinal 
contents  of  cases  in  which  I  made  the  autopsy,  I  have  never  seen  any 
formation  of  black  pigment  such  as  Dr.  Gibier  described  in  his  first 
communication  to  the  French  Academy  of  Sciences  with  reference  to 
the  bacillus  under  consideration. 

The  morphology  of  Gibier's  bacillus  is  shown  in  Figs.  1  and  2,  PI.  iv. 

It  is  an  actively  motile  bacillus  with  round  ends,  which  varies  con- 
siderably in  length,  being  sometimes  short  oval,  and  again,  in  the  same 
culture,  long  oval;  or  it  may  grow  out  into  a  flexible  filament  of  con- 
siderable length.  In  recent  cultures  the  bacilli  are  often  united  in 
pairs,  and  are  deeply  stained  by  an  aqueous  solution  of  fuchsin,  or 
methylene  blue;  in  cultures  which  are  several  days  old,  or  in  recent 
cultures  when  the  stained  preparation  is  washed  in  alcohol,  the  ends  of 
the  rods  are  commonly  more  deeply  stained  than  the  central  portion. 
My  photomicrograph  is  from  the  surface  of  an  agar  culture  12  days 
old,  and  shows  some  of  the  bacilli  of  recent  development  deeply  stained, 
while  others  in  the  same  field  are  but  faintly  stained. 

This  bacillus  liquefies  gelatine,  as  shown  in  Figs.  5,  6,  and  7,  PI.  iv. 

At  the  end  of  24  hours,  at  a  temperature  of  20°,  to  22°  C,  there  is  an 
abundant  development  along  the  line  of  puncture  and  commencing 
liquefaction  at  the  surface.  Later  the  liquefaction  is  funnel-shaped, 
and  there  is  an  opaque  white  central  core  along  the  line  of  puncture 
■with  liquefied  gelatine  around  it.  Liquefaction  progresses  most  rapidly 
at  the  surface,  and  in  the  course  of  3  or  4  days  the  upper  portion  of 
the  gelatine,  for  the  distance  of  half  an  inch  or  more,  is  completely 
liquefied,  and  an  opaque  white  mass,  composed  of  bacilli,  rests  upon 
the  surface  of  the  unliquefied  portion. 

In  gelatine  roll-tubes  the  young  colonies  upon  the  surface  are  trans- 
parent and  resemble  somewhat  small  fragments  of  broken  glass  (see 
Fig.  3,  PI.  IV);  later  liquefaction  occurs  rapidly,  and  the  colonies  are 
as  seen  in  Fig.  4,  PI.  iv.     Deep  colonies  in  gelatine  roll-tubes  or  at  the 


170 


ETIOLOaV    AND    PREVENTION    OF    YELLOW    FEVEIi. 


bottom  of  gelatine  stick- cultures  are  spherical,  translucent,  and  of  a 
pale  straw  color. 

Upon  tbe  surface  of  nutrient  agar  it  grows  rapidly,  forming  a  rather 
thin,  translucent,  shining,  white  layer,  which  covers  the  entire  surface 
at  the  end  of  2  or  3  days  at  a  temperature  of  20°  C.     (See  Fig.  3,  PI.  xx.) 

Upon  potato  the  growth  is  rapid  and  thin,  covering  the  entire  sur- 
face, and  is  of  a  pale  yellow  color. 

This  bacillus  grows  at  a  comparatively  low  temjierature,  and  its 
vitality  is  not  destroyed  by  exposure  for  an  hour  and  a  half  in  a  freez- 
ing mixture  at  15°  C.  below  zero  (5°  F.). 

Decided  growth  occurred  in  a  stick  culture  in  gelatine  exposed  in 
Baltimore  during  the  month  of  January  in  an  attic  room  (January  7  to 
29).  During  the  22  days  of  exposure  the  highest  temperature,  taken  at 
9  a.  m.  each  day,  was  11°  C,  and  the  lowest,  2°  (J.  At  a  temperature 
of  ICP  to  20^  0.  development  in  a  favorable  culture  medium  is  rapid. 

There  is  no  evidence  that  this  bacillus  forms  spores ;  cultures  are 
sterilized  by  exposure  to  a  temperature  of  60°  C.  for  10  minutes. 

Coagulated  blood  serum  is  liquefied  by  this  bacillus.  It  retains  its 
vitality  for  a  long  time  in  old  cultures,  having  grown  freely  when 
replanted  at  the  end  of  a  year  from  a  hermetically  sealed  tube  contain- 
ing a  i)ure  culture  in  blood  serum. 

My  experiments  on  animals  are  given  below  in  tabular  form  t 


Animal. 

Ko. 

Size. 

Date. 

Where  injected. 

Amount. 

Result. 

1888. 

Eabbit 

n 

May  28 

Cavity  of  abdomen . 

culture. 

Do 

27 

Very  small.. 

Aug.  16 

Subcutaneous 

3  CO.  bouillon 
cnlture. 

Do. 

Do 

28 

....do 

Aug.  le 

....do 

6  CO.  bouillon 
culture. 

Found  dead  at  end 
of  16  hours. 

Do 

29 

....do  

Aug.  16 

Cavity  of  abdomen . 

3  cc.  bouillon 
culture. 

Do. 

Do 

30 

420  grams... 

Aug.  20 

....do  ......... 

Died   at   end   of  48 

hours. 

Do  

ril 

425  grams. .. 

Aug.  20 

Died    at    end   of    2 

culture. 

hours. 

Do 

32 

420  grams... 

Aug.  20 

....do  

6  cc.  bouillon 
culture. 

Found  dead  at  end 
of  20  hours. 

Do 

35 

400  grams... 

Sept.    4 

Cavity  of  abdomen. 

2   cc.    gelatin 
culture. 

Do. 

Do 

+6 

Largo 

Sept.  11 

....do  

4   cc.    gelatin 

Found  dead  at  end 

culture. 

of  4  hours. 

Do 

52 

Small 

Sept.  24 

.-..do 

3   cc.    gelatin 
culture. 

Died  at  end  of  3 
hours. 

Do 

53 

....do  

Sept.  24 

■-do 

....do 

Died  at  end  of  4^ 
hours. 

Do 

55 

Large ... 

Sept.  27 

do 

2J  cc.  gelatin 
culture. 

Eecovered, 

Do 

5(i 

Small 

Sept.  27 

....do  

IJt   cc.  gelatin 

Found  dead  at  end 

culture. 

of  20  hours. 

ETIOLOGtY    Al^D    PREVENTION    OE    YELLOW   FEVER. 


171 


No. 


Size. 


Date. 


Where  injected. 


Amount. 


Ee.sult. 


Do 

Guinea  pigs 

Do 

Do 


Small 

.')55  grams . . . 
720  grams... 
750  grams... 
874  grama... 
720  grama . . . 


1,  350  grams 
1,620  grams 


73     .-^OO  grams. 


74  !  200  grams... 

75  1,800  grama. 


1,  750  grama 

2,  000  grams. 
...do 


550  grams... 
480  grama.. . 
470  grams . . . 
1,750  grams. 
1, 115  grams 
1,015  grams 
1,  735  grams. 

1,  792  grams 
1,770  grams 

1,887  grams 

2,  430  grams 

1,  940  grams 


1888. 

Nov.  5 

Dec.  5 

Dec.  12 

Dec.  1.5 

Dec.  20 

Dec.  18 

Dec.  18 

1889. 

Jan.  2 

Jan,  2 

Jan.  3 

Jan.  3 

Jan.  3 

Jan.  4 

Jan.  4 

Jan.  8 

Jan.  8 

Jan.  8 

Jan.  8 

Jan.  8 

Jan.  9 

Jan.  9 

Jan.  15 

Jan.  15 

Jan.  15 

Jan.  15 

Jan.  15 

Jan.  15 

1888. 

May  28 

Aug.  10 

Aug.  10 


Subcutaneous 

...do 

...do 

Cavity  of  abdomen. 

...do 

Small  intestine  — 

...do 

Ear  vein 

...do 

Cavity  of  abdomen 

...do 

...do 


Ear  vein. 


...do 

Cavity  of  abdomen. 

...do 

...do 

.J. do 

...do  

...do  

...do 

...do  


...do 

...do 


...do 
...do 


2  cc.   gelatin 
culture. 

...do 

3  cc.   gelatin 
culture. 

1    cc.   gelatin 

culture. 
^   cc.   gelatin 

culture. 
J    cc.    gelatin 

culture. 
J    cc.   gelatin 

culture. 
3  drops  gela- 
tin culture. 
i    cc.    gelatin 

culture. 
1    cc.   gelatin 

culture. 

...do  

J    cc.   gelatin 

culture. 

3  drops  bouil- 
lon culture. 

....do    

1  cc.  gelatin 
culture. 

4  cc.  bouillon 
culture. 

2  cc.  bouillon 
culture. 

1  cc.  bouillon 

culture. 
1    cc.   gelatin 

culture. 
1  cc.  bouillon 

culture. 
^  cc.  bouillon 

culture. 

3  cc.   gelatin 
culture. 

....do 

^    cc.   gelatin 
culture. 

....do 

....do  


...do  

...do 

...do  

...do  


4    cc.   gelatin 

culture. 
J  cc.  bouillon 

culture. 
1  cc.  bouillon 

culture. 
....do 


Recovered. 

Found  dead  at   end 

of  20  hours. 
Died    at   end   of   24 

hours. 
Found  dead  at  end 

of  20  hours. 
Found     dead     next 

moTuing. 
Eeault  negative. 

Do. 

Found     dead     next 

morning. 
Died  at  end    of    2J 

houra. 
Died    at    end   of    7 

houra. 
Do. 
Reault  negative. 

Do. 

Do. 

Found  dead  at  end 
of  20  houra. 
Do. 

Do. 

Do. 

Do. 

Result  negative. 

Do. 

Died    at    end   of    7 

hours. 
Died  in  3  hours. 
Died  in  7  houra. 

Died  in  3  hours. 
Found     dead     next 

morning. 
Died  in  3  hours. 

Result  negative. 

Do. 

Do. 


172 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


Animal. 

No. 

Guinea  pig  .. 

23 

Do 

32 

Do 

33 

White  rats... 

1 

Do 

2 

Do 

3 

Size. 


Date. 


1889. 
Aug.  13 

Sept.  27 

Sept.  27 
Aug.  23 

Aug.  23 

Aug.  23 


Where  injected. 


Cavity  of  abdomen 
....do  


...do 

Subcutaneous 


...do 
...do 


Amount. 


8    cc.   gelatin 
culture. 

2  cc.   gelatin 
culture. 

....do 

3  cc.  bouillon 
culture. 

5  cc.  bottillon 

culture. 
....do 


Result. 


Died  next  morning 

Do. 

Eesult  negative. 
Do. 

Do. 

Do. 


These  experiments  show  that  the  bacillus  of  Gibier  is  very  pathogenic 
for  rabbits  when  injected  into  the  cavity  of  the  abdomen  in  quantitit>s 
of  1  cubic  centimetre  or  more,  that  it  is  less  pathogenic  for  guinea-pigs, 
and  is  not  pathogenic  for  white  rats  when  injected  subcutaneously. 
Gelatine  cultures  seem  to  possess  more  intense  pathogenic  power  than 
bouillon  cultures,  and  cultures  from  the  blood  of  an  animal  recently 
dead  as  the  result  of  an  inocculation  are  more  potent  than  those  from 
my  original  stock  which  had  not  been  passed  through  a  susceptible 
animal. 

The  mode  of  death  in  rabbits  is  quite  characteristic.  A  couple  of 
hours  after  receiving  in  the  cavity  of  the  abdomen  2  or  3  cubic  centi- 
metres of  a  liquefied  gelatine  culture  the  animal  becomes  quiet  and  in- 
disposed to  eat  or  move  about.  Soon  after  it  becomes  somnolent,  the 
head  drooping  forward  and  after  a  time  resting  between  the  front  legs 
with  the  nose  on  the  floor  of  its  cage.  It  can  be  roused  from  this  con- 
dition, and  raises  its  head  in  an  indifferent  and  stui)id  way  when  pushed 
or  shaken,  but  soon  drops  off  again  into  a  profound  sleep.  Frequently 
the  animals  die  in  a  sitting  position  with  their  nose  resting  upon  the 
floor  of  the  cage  between  the  front  legs.  I  have  not  seen  this  lethargic 
condition  produced  by  inoculations  with  any  other  microorganism. 
Convulsions  sometimes  occur  at  the  moment  of  death. 

The  time  of  death  depends  upon  the  potency  of  the  culture  and  its 
quantity  as  compared  with  the  size  of  the  animal. 

With  a  full  dose  of  3  to  4  cubic  centimetres  of  a  liquefied  gelatine 
culture  death  commonly  occurs  in  from  3  to  7  hours. 

The  rapidity  with  which  death  occurs  when  a  considerable  quantity 
of  a  liquefied  gelatine  culture  is  injected  into  the  cavity  of  the  abdomen, 
and  the  somnolence  which  precedes  death,  give  rise  to  the  supposition 
that  the  lethal  effect  is  due  to  the  presence  of  a  toxic  chemical  substance, 
rather  than  to  a  multiplication  of  the  bacillus  in  the  body  of  the  animal. 
And  this  view  is  supported  by  the  fact  that  animals  frequently  recover 
when  the  dose  administered  is  comparatively  small,  and  especially 
when  it  is  injected  subcutaneously.     I  have  made  a  few  exijeriments 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  173 

with  cultures  sterilized  by  heat  for  the  purpose  of  testing  the  truth  of 
this  supposition.     The  results  are  given  below: 

September  1,  1888. — iDJected  subcntaneonsly  into  rabbit  No.  34,  15  cubic  centimetres 
sterilized  bouillon  culture  of  Gibier's  bacillus.  Temperature  at  11  a.  m.,  before  inocu- 
lation, 102.6°  ;  temperature  at  12:30,  after  inoculation,  103.5° ;  at  2  p.  m.,  104.3°  ;  at  4 
p.m. ,105. 8°;  at6p.  m.,  105°.  September2,  9a.  m.,  temperature  104°.  Animal  appears 
well.     Result  negative  except  for  the  rise  of  temperature  noted. 

September  6,  12  m. — Injected  into  cavity  of  abdomen  of  small  rabbit  (weight  400 
grammes),  5  cubic  centimetres  sterile  gelatine  culture  of  Gibier's  bacillus.  Found 
dead  September  8^  at  8  a.  m.  Liver  dark-colored;  stomach,  spleen,  and  intestine 
normal. 

Sepiemher  4,  11:30  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  No.  35  (weight 
400  grammes),  2  cubic  centimetres  sterilized  gelatine  culture  of  Gibier's  bacillus.  Re- 
sult negative. 

December  20,  1888. — Injected  into  cavity  of  abdomen  of  rabbit  66  (weight  972 
grammes),  4  cubic  centimetres  sterilized  gelatine  culture  of  Gibier's  bacillus,  at  10 
a.  m.  Temperature  before  injection,  101°  F. ;  temperature  at  1  o'clock,  101°.  At  2:  30 
p.m.  injected  a  second  dose  of  5  cubic  centimetres  sterilized  culture  into  cavity  of 
abdomen.  At  3:30  the  animal  is  somnolent.  At  4:  30  p.  m.  injected  4  cubic  centi- 
metres of  same  culture;  temperature  at  4:30,  100. .5°  F.  At  5  p.  m.  the  animal  seems 
feeble  and  somnolent;  temperature  at  6  p.  m.,  102.2°,  December  21,  10:30  a.  m.,  the 
animal  seems  better.  Injected  into  cavity  of  abdomen  5  ciibic  centimetres  of  the 
same  sterile  gelatine  culture.  December  29,  the  animal  remains  in  good  health  and 
was  injected  in  the  cavity  of  the  abdomen  with  1  cubic  centimetre  liquefied  gelatine 
culture,  not  sterilized,  to  test  protective  value  of  previous  inoculations.  Result  of 
injection  negative. 

My  time  having  been  fully  occupied  with  other  experimental  work  I 
have  not  yet  followed  up  this  experiment  upon  the  protective  value  of 
inoculations  with  sterilized  cultures,  but  infer  from  the  above  experi- 
ment that  the  result  of  a  careful  experimental  inquiry  would  establish 
the  fact  that  a  certain  degree  of  immunity,  at  least,  may  be  conferred 
by  inoculations  with  culture  fluids  sterilized  by  heat. 

The  temperature  of  rabbits  which  receive  a  lethal  dose  of  a  culture 
of  this  bacillus  falls  below  the  normal  sometime  oefore  death.  This  is 
shown  by  the  following  notes  : 

August  20,  10:45  a.  m. — Injected  subcutaneously  into  rabbit  32  (weight  420  grammes), 
6  cubic  centimetres  bouillon  culture  of  Gibier's  bacillus.  Temperature  just  before 
injection,  102°  F.  ;  temperature  at  12  o'clock,  10.3° ;  at  1  o'clock,  103°  ;  at  4  o'clock 
p.  m.,  99°.  Animal  appears  feeble  and  dull ;  temperature  at  6:15  p.  m.,  99°.  Found 
dead  next  morning. 

September  24,  10:30  a.m. — Two  small  rabbits,  Nos.  51  and  52,  injected  in  cavity  of 
abdomen  with  3  cubic  centimetres  liquefied  gelatine  culture  of  Gibier's  bacillus. 
At  12:30  both  animals  are  very  lethargic  and  somnolent ;  temperature  in  rectum,  99° ; 
temperature  at  1:30  p.  m.,  95°.  One  died  at  1:30  and  one  at  3  p.  m.,  both  in  convul- 
sions. 

January  15,  1889,  10:30  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  No.  86 
(weight  1,735  grammes),  3  cubic  centimetres  liquefied  gelatine  culture  of  Gibier's  bacil- 
lus. At  2 p.m.  the  animal  is  lethargic  ;  temperature,  99.8°  F.  ;  temperature  at  2:45 
p.  m.,  98°.  Died  in  convulsions  at  5:30  p.  m.  Temperature  immediately  after  death 
in  rectum,  96°. 

January  15,  1889,  10:30  a.  m.— Injected  into  cavity  of  abdomen  of  rabbit  No.  88 
(weight  1,770  grammes);  one-half  of  a  cubic  centimetre  gelatine  culture  bacillus  g,  from 
feces  56,  Decatur  (Gibier's  bacillus).  Temperature  at  2  p.  m.,  100.2°  ;  is  lethargic. 
Temperature  at  2:45,  98.5°.     Dying  at  5:30  p.  m.  ;  temperature,  96.6°.     Died  at  6  p.m. 


174     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

In  all  cases  in  which  death  occurs,  even  when  but  a  few  hours  have 
elapsed  since  the  inoculation  was  made,  I  have  recovered  the  bacillus 
in  cultures  made  from  blood  obtained  from  the  heart  or  the  interior  of 
the  liver,  and,  as  stated,  these  cultures  appear  to  have  a  greater  viru- 
lence than  those  not  passed  through  the  rabbit. 

In  sections  of  the  liver  and  kidney  stained  with  Loeffier's  solution  of 
methyline  blue  the  bacilli  are  seen,  and  are  often  in  rather  long  jointed 
filaments. 

INJECTIONS  INTO   THE  INTESTINE. 

Upon  my  return  from  Havana  in  1888  I  admitted  the  possibility  that 
this  bacillus  might  have  an  etiological  relation  to  yellow  fever,  although 
my  culture  experiments  in  10  cases  had  only  demonstrated  its  presence 
in  the  contents  of  the  intestine  3  times.  I  therefore  made  a  variety  of 
experiments  with  it,  and  among  others  the  following: 

November  27,  1888,  3^,  m. — Injected  into  lumeu  of  intestine  of  dog  No.  2,  small 
black  and  tan,  2  cubic  centimetres  liquefied  gelatine  culture  of  Gibier's  bacillus. 
Animal  died  of  peritonitis  from  the  operation  at  end  of  36  hours;  liver  and  kidney 
normal. 

November  27, 1888. — Injected  into  lumen  of  intestine  of  dog  No.  4,  2  cubic  centimetres 
liquefied  gelatine  culture  of  Gibier's  bacillus.  Temperature  taken  for  8  days  showed 
no  notable  departure  from  the  normal,  and  the  animal  made  a  good  recovery. 

December  4,  1888. — Injected  into  lumen  of  intestine  of  dog  No.  5,  2  cubic  centimeters 
liquefied  gelatine  culture  of  Gibier's  bacillus.  Temperature  taken  for  7  days  showed 
no  notable  departure  from  the  normal,  and  the  animal  remained  well. 

December  4,  1888. — Injected  into  lumen  of  intestine  of  dog  No.  6,  2  cubic  centimetres 
liquefied  gelatine  culture  of  Gibier's  bacillus.  Temperature  taken  for  7  days  showed 
no  notable  departure  from  the  normal,  and  the  animal  remained  well. 

Decem&er  18, 1888. — Injectedintolumenof  intestine  of  rabbit  69  (weight  720grammes), 
one-half  of  a  cubic  centimetre  licjuefied  gelatine  culture  of  Gibier's  bacillus.  Tbe  result 
was  negative.  On  the  29th  of  December  1  cubic  centimetre,  liqeufied  gelatine  culture 
was  injected  beneath  the  skin  of  this  rabbit.  The  animal  was  found  dead  next  morn- 
iuo',  still  warm;  diffuse  cellulitis  from  point  of  inoculation;  stomach  and  intestine 
enormously  distended  with  gas ;  spleen  slightly  enlarged ;  intestine  glued  together 
and  to  -walls  of  abdomen  by  adhesions  at  point  of  previous  operation. 

December  18,  1888. — Injected  into  lumen  of  intestine  of  rabbit  No.  70  (weight  720 
grammes),  one-half  of  a  cubic  centimetre  liquefied  gelatine  cultureof  Gibier's  bacillus. 
Result  negative. 

The  pathological  appearances  observed  in  rabbits  which  succumb  to 
a  lethal  dose  of  a  culture  of  this  bacillus  are  not  very  marked ;  the 
spleen  is  sometimes  enlarged,  but  otherwise  the  abdominal  viscera  ap- 
j)ear  to  be  normal.  When  the  injection  is  made  subcutaneously  a 
diffuse  cellulitis,  extending  from  the  point  of  inoculation,  is  frequently 
observed. 

THE  BACILLUS  OF  LACERDA  AND  BABES. 

In  1883  Dr.  Lacerda,  of  Eio  de  Janeiro,  having  discovered  what  he 
believed  to  be  microorganisms  in  the  liver  and  kidney  of  yellow-fever 
cases,  sent  some  of  the  material  to  Paris,  to  Dr.  Babes.    This  bacteri- 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  175 

ologist  demonstrated  the  presence  of  a  microbe  in  this  material  and 
described  it  as  follows  : 

The  filaments  appear  uuited  and  homogeneous  with  an -amplification  of  600  diame- 
ters, hut  with  a  high  power,  one-twelfth  hom.im.,  or  No.  12  of  Vcrick  (which  corre- 
sponds with  the  one-eighteenth  of  Zeiss),  one  can  assure  himself  that  these  filaments 
are  composed  of  elliptical  grains,  almost  cylindrical,  arranged  in  pairs,  forming  little 
groups  in  which  they  are  united  by  an  intermediary  pale  substance.  The  filaments 
are  thus  composed  of  diplococci,  or,  if  one  wishes,  of  very  short  rods  with  terminal 
spores. 

Dr.  Lacerda  has  described  the  organism  referred  to  as  in  filaments 
which  branch  dichotomously,  and  believes  this  branching  to  be  a  con- 
stant and  distinctive  characteristic  of  the  parasite,  which  he  accepts  as 
the  veritable  yellow-fever  microbe.  He  is  without  doubt  mistaken. 
The  apparent  branchiug  of  the  filaments  which  he  has  described  and 
drawn,  and  which  he  showed  me  in  some  of  his  preparations  at  the  time 
of  my  visit  to  Eio,  is  due  simply  to  the  accidental  juxtaposition  of  the 
torula-like  chains.  He  is  also  mistaken  in  supposing  that  this  organ- 
ism is  only  to  be  satisfactorily  demonstrated  by  Gram's  method  of 
staining.  My  friend,  Dr.  Goes,  shared  this  belief  at  the  time  of  my 
visit  to  Eio,  but  I  demonstrated  to  him  the  facility  with  which  the 
organism  may  be  stained  with  a  solution  of  methyliue  blue,  upon  sec- 
tions which  he  made  for  me  from  material  in  Dr.  Lacerda's  laboratory. 
Since  my  return  to  Baltimore  I  have  made  numerous  sections  from  the 
same  material,  and  find  no  difficulty  in  staining  the  organism  present 
in  the  tissues  with  methyliue  blue  or  with  fuchsin. 

Babes  himself  has  renounced  the  idea  that  this  microorganism  bears 
an  etiological  relation  to  the  disease  under  consideration.  In  the  sec- 
ond edition  of  "  Les  Bacteries  "  he  says  : 

Since  these  researches  we  have  had  the  opportunity  to  examine  several  series  of 
sections  from  yellow  fever.  First,  the  liver  and  kidney  of  two  individuals  dead  from 
this  malady,  collected  by  Dr.  Alvarez,  were  examined  in  the  laboratory  of  patholog- 
ical anatomy  of  the  faculty  of  Paris,  without  any  bacteria  having  been  found  ;  second, 
material  from  three  cases  of  yellow  fever  which  Koch  was  kind  enough  to  confide  to 
one  of  us.  In  these  last  three  cases,  notwithstanding  the  most  scrupulous  research, 
and  notwithstanding  the  adidce  of  Koch,  it  was  impossible  to  find  the  little  chains 
in  the  brain,  the  kidneys,  the  liver,  and  the  spleen.  We  must  suppose,  then,  that  in 
yellow  fever,  as  in  other  infectious  maladies,  microbes  are  only  found  in  the  paren- 
chymatous organs  in  certain  cases,  and  not  in  all.  The  question  whether  these  mi- 
croorganisms really  constitute  the  cause  of  the  malady,  or  simply  a  complication,  is 
consequently  not  resolved. 

The  fact  that  this  microorganism  is  not  present  in  the  liver  and  kid- 
ney of  forty  cases  in  which  I  have  made  autopsies  in  Havana,  is  ample 
evidence  that  its  presence  in  the  material  from  Dr.  Lacerda's  laboratory, 
which  was  sent  to  Babes,  was  accidental,  and  bore  no  relation  to  the 
etiology  of  the  malady. 

I  shall  submit,  in  connection  with  this  report,  a  large  series  of  slides 
showing  thin  sections  of  these  organs  stained  by  methods  which  demon- 
strate the  presence  of  this  bacillus  in  material  containing  it.    Various 


176  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

microorganisms  are  present  in  some  of  these  cases  and  have  been  re- 
ferred to  elsewhere,  but  neither  Dr.  Councilman  nor  myself,  after  a  care- 
ful search,  have  been  able  to  find  this  bacillus  in  chains  in  the  numer- 
ons  sections  examined  by  us.  I  shall  submit  at  the  same  time  a  number 
of  slides  stained  by  the  same  methods,  and  showing  thin  sections  from 
material  brought  by  me  from  Dr.  Lacerda's  laboratory  belonging  to  the 
cases  ir  which  this  bacillus  was  first  found,  and  in  these  the  bacillus  is 
well  shown.  There  is,  therefore,  no  question  that  its  presence  would 
have  been  demonstrated  in  sections  from  my  Havana  material  stained 
in  the  same  way  if  it  were  really  present. 

I  insist  upon  this  point  because  Dr.  Frank  Billings,  in  a  letter  dated 
March  6,  1889,  published  in  the  "Medical  Register"  of  Philadelphia, 
states  that  he  has  found  this  bacillus  in  material  from  seven  cases. 
He  says: 

Suffice  it  to  say  that  each  has  been  carefully  examined,  and  in  each  the  same  orj^an- 
ism  found  as  described  by  me,  March  last,  and  in  the  Register  last  year,  acd  described 
by  Babes  in  1S85,  and  in  only  one  specimen  is  there  any  pollution,  and  that  but  slight, 
of  a  few  specimens  of  a  large  bacillus. 

Dr.  Billings  obtained  his  material  through  my  friend  Dr.  D.  M.  Bur- 
gess, of  Havana,  and  it  so  happens  that  the  material  from  two  of  the 
six  cases  sent  him  by  Dr.  Burgess  was  from  autopsies  made  by  myself 
at  the  military  hospital.  At  Dr.  Burgess's  request  I  permitted  him  to 
take  material  for  Dr.  Billings  at  these  two  autopsies  which  he  assisted 
me  in  making.  At  the  same  time  I  preserved  material  in  alcohol  and 
in  sealed  tubes  for  making  cultures,  as  was  my  i)ractice. 

The  two  cases  referred  to  are  those  given  in  Dr.  Billings'  list  as  fol- 
lows: 

5.  Soldier,  died  of  yellow  fever  in  military  hospital,  Havana,  June  3,  1888. 
Autopsy  5  hours  after  death. 

6.  Soldier,  died  on  June  6,  1883.    Autopsy  3  hours  after  death. 

These  are  the  two  last  autopsies  made  by  me  in  Havana,  in  1888,  and 
are  numbered  in  my  list  9  and  10.  My  notes  of  these  cases  are  as  fol- 
lows: 

Autopsy  No.  9,  June  3,  1888:  Soldier  in  military  hospital;  sick  5  days;  autopsy  5 
hours  after  death.  Collected  material  from  liver,  kidney,  stomach,  and  intestine, 
blood  from  heart,  and  urine  from  bladder.  Numerous  colonies  of  bacillus  a  developed 
in  cultures  from  blood,  liver,  urine,  and  kidney. 

Autopsy  No.  10,  May  6,  1888  :  Soldier  in  military  hospital ;  sick  5  days  ;  autopsy  1 
hour  and  40  minutes  after  death.  (Dr.  Burgess  is  mistaken  in  giving  the  time  as  3 
hours.)  Collected  material  from  liver,  kidney,  stomach,  and  intestine,  blood  from 
heart,  and  urine  from  bladder.  No  development  in  cultures  from  blood,  liver,  kid- 
ney, or  urine. 

Since  my  return  from  Cuba  numerous  sections  have  been  made  from 
the  material  preserved  in  alcohol  from  these  two  cases.  These  sections 
have  been  made  by  myself,  by  my  assistant,  Dr.  Emilio  Martinez,  and 
by  my  friend  Dr.  James  B.  Eeeves  of  Chattanooga, 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  177 

The  sections  from  case  9  show  the  same  baciUus  which  was  demon- 
strated to  be  present  in  great  numbers  in  the  blood,  liver,  and  kidney 
by  my  cultures  made  from  fresh  material.  This  is  my  bacillus  a,  which 
by  a  careful  research  I  have  shown  to  be  identical  with  the  bacterium 
coli  commune  of  Escherich. 

As  stated  elsewhere,  this  is  the  microorganism  which  is  most  fre- 
quently present  in  yellow-fever  tissues,  as  shown  both  by  the  culture 
method  and  in  stained  sections  of  material  preserved  in.  alcohol.  It  is 
longer  than  the  Babes  bacillus  and  is  not  united  in  chains.  No  doubt 
Dr.  Billings  found  the  same  bacillus  in  his  material  from  the  same 
case,  for  it  is  present  in  very  great  abundance  and  is  easily  stained  by 
the  usual  methods. 

In  case  10  my  cultures  gave  a  negative  result,  but  in  my  sections 
from  the  kidney  and  in  those  mounted  for  me  by  Dr.  Eeeves  there  is 
present  a  micrococcus.  This  is  an  exceptional  case  in  this  regard,  being 
the  only  one  in  which  I  have  encountered  micrococci.  They  are  present 
in  some  of  the  sections  onl}^,  in  masses  blocking  up  the  capillaries. 
Dr.  Billings  seems  not  to  have  found  them,  as  he  says  "in  onlj^  one 
specimen  is  there  any  pollution,  and  that  but  slight,  of  a  few  specimens 
of  a  large  bacillus." 

Dr.  Billings  goes  on  to  say : 

Furtliermore,  the  organism  is  in  the  blood  in  every  section  and  in  great  numbers, 
every  authority  to  the  contrary.  Now  I  do  hold,  also  against  all  contradiction,  that 
in  such  a  disease  as  yellow  fever,  where  one  finds  one  organism  closely  and  sharply 
in  many  sections  and  all  parts  of  these  sections,  and  in  all  these  sections  but  two 
specimens  of  another,  that  that  organism  is  the  cause  of  the  disease  of  which  the 
individual  died.  Here  we  have  seven  "  undoubted  cases  of  yellow  fever,"  in  which 
this  one  organism  is  present  in  immense  numbers,  so  plentiful  that  I  boldly  say  it  is 
want  of  technical  ability  both  as  bacteriologists  and  microscopists  that  others  have 
not  found  them.  I  will  say  further,  that  it  is  the  same  organism  recently  seen  by 
Dr.  Reeves,  of  Tennessee,  but  where  his  material  came  from  I  do  not  know,  but  I 
have  one  of  his  slides. 

Is  it  then  want  of  technical  ability  that  has  prevented  Babes  from 
finding  a  bacillus,  first  demonstrated  by  him  in  the  Eio  material,  in 
other  material  carefully  searched  in  order  to  confirm  his  discovery!  I 
have  already  quoted  what  he  says,  but  repeat  the  quotation  : 

Since  these  researches  we  have  had  the  opportunity  to  examine  several  series  of 
sections  of  yellow  fever  ;  first,  the  liver  and  kidney  of  two  individuals  dead  from  this 
malady,  collected  by  Dr.  Alvarez,  were  examined  in  the  laboratory  of  Pathological 
Anatomy  of  the  Faculty  of  Paris,  without  any  bacteria  having  been  found;  second, 
material  from  three  cases  of  yellow  fever  which  Koch  was  kind  enough  to  confide  to 
one  of  us.  In  these  last  three  cases,  notwithstanding  the  advice  of  Koch,  it  was 
impossible  to  find  the  little  chains  in  the  brain,  the  kidneys,  the  liver,  and  the  spleen. 

I  may  refer  here  to  my  researches  prior  to  my  visit  to  Brazil,  and 
quote  from  my  previous  report: 

Desiring  to  supplement  the  observations  made  in  Havana,  in  1879,  by  further  re- 
searches, I  wrote  to  my  friend  Dr.  Daniel  M.  Burgess,  of  Havana,  some  time  during 
the  summer  of  1834,  requesting  him  to  obtain  for  me  small  pieces  of  liver,  kidney, 
4067 12 


178  ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER. 

and  stomacli  froui  oue  or  more  typical  cases  of  yellow  fever.  I  made  it  an  essential 
condition  that  tlie  antoj^sies  should  be  made  within  an  hoar  or,  at  the  outside,  two 
hours  after  death,  so  that  there  might  be  no  question  of  post-mortem  changes.  Small 
pieces  of  the  organs  named  were  to  be  put  at  ouce  into  a  large  quantity  of  strong 
alcohol.  In  conniliance  witb  my  request  Dr.  Burgess  obtained  and  forwarded  to  me 
material  from  two  cases,  which  reached  me  in  good  condition,  and  upon  microscopic- 
examination  the  liver  and  kidueys  showed  the  pathological  changes  constantly  found 
in  the  disease  in  question.  During  the  winter  of  1884  I  mounted  numerous  thin 
sections  from  this  material,  stained  with  various  aniline  colors.  In  none  of  them  did 
I  find  any  microorganisms,  except  upon  the  surface  of  the  mucous  membrane  in  sec- 
tions of  the  stomach,  where  various  organisms — bacilli  and  micrococci — were  to  be 
seen  in  properly  stained  sections.  These  were,  however,  only  upon  the  surface,  at- 
tached to  the  epithelium,  or  mingled  with  a  granular  debris  adhering  to  the  surface 
of  the  mucous  membrane.  In  the  autumn  of  1885,  during  a  visit  to  Dr.  Koch's  labor- 
atory in  Berlin,  I  had  an  opportunity  to  avail  myself  of  the  suggestions  and  valuable 
assistance  of  the  master  in  bacteriology,  and  again  studied  the  material  which  Dr. 
Burgess  had  sent  me  from  Havana  by  the  various  methods  of  staining  considered  to 
be  most  useful  in  such,  a  research.  At  the  request  of  Dr.  Koch  I  was  assisted  by  Dr. 
Carl  Seitz,  who  was  at  the  time  engaged  upon  his  studies  of  the  typhoid  bacillus, 
and  was  an  expert  in  staining  and  mounting  thin  sections  of  the  tissues.  Dr.  Seitz 
and  myself  examined  numerous  sections  of  liver  and  kidney  stained  by  various 
methods,  with  an  entirely  negative  result  so  far  as  the  j)resence  of  microorganisms 
was  concerned.  After  my  return  to  Baltimore,  in  1886,  I  again  made  numerous  sec- 
tions from  the  same  material  and  stained  them  with  Lceffler's  alkaline  solution  of 
methyline  blue,  which  we  had  also  used  in  Dr.  Koch's  laboratory,  and  with  other 
aniline  colors,  but  without  any  better  success. 

The  following  summer  I  went  to  Brazil,  where  I  had  no  difficulty  in 
demonstrating  the  presence  of  Babes  bacillus  in  material  containing  it, 
preserved  in  Dr.  Lacerda's  laboratory,  by  exactly  the  same  method  of 
staining  (Loefiier's  solution)  which  had  given  me  a  negative  result  with 
the  material  examined  in  Koch's  laboratory  and  in  Baltimore. 

Finally,  Dr.  Billings  accords  to  Dr.  Eeeves  of  Chattanooga  the  tech- 
nical skill  necessary  to  demonstrate  the  presence  of  this  bacillus.  He 
says :  "  I  will  say  further  that  it  is  the  same  organism  recently  seen  by 
Dr.  Eeeves,  of  Tennessee,  but  where  his  material  came  from  I  do  not 
know,  but  I  have  one  of  his  slides." 

This  statement  has  induced  me  to  place  in  Dr.  Eeeves  hands  material 
from  a  series  of  twenty-five  cases.  He  has  made  for  me  from  this  ma- 
terial a  series  of  slides  which  certainly  exhibit  technical  skill  of  a  high 
order  5  they  are  stained  especially  to  demonstrate  the  presence  of  micro- 
organisms, and  various  bacilli  are  present  in  those  which  represent 
certain  cases.  These  I  have  described  in  the  jjroper  place,  but  they  do 
not  show  the  presence  of  the  bacillus  of  Babes  which  Dr.  Billings  says 
is  present  in  all  his  material  "in  every  section  and  in  great  numbers," 

At  my  request  Dr.  Councilman  has  gone  over  these  slides  of  Dr. 
Eeeves  with  great  care  and  the  result  of  his  examination  fully  accords 
with  my  own.  Moreover,  Dr.  Eeeves'  sections  show  bacilli  in  the  same 
cases  as  do  those  mounted  by  myself  and  my  laboratory  assistant. 
They  have  no  advantage  over  my  own  in  the  demonstration  of  micro- 
organisms present. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER. 


179 


With  reference  to  the  slide  mounted  by  Dr.  Eeeves  which  Dr.  Bill- 
ings has  seen,  I  have  no  doubt  it  is  one  of  those  made  by  him  from  my 
Decatur  material.  I  made  but  three  autopsies  in  Decatur,  and  the  ma- 
terial preserved  from  these  was  placed  in  alcohol  which  was  sent  me 
in  a  tin  can  from  a  neighboring  town.  I  have  always  suspected  that 
this  alcohol  was  not  of  sufficient  strength  to  properly  preserve  the 
tissues.  On  my  way  home  from  Decatur  I  stopped  over  for  a  day  to 
see  my  friend.  Dr.  Eeeves,  who  begged  me  to  give  him  some  of  my 
yellow- fever  material  for  study.  Upon  opening  the  box  containing  it 
I  found  that  one  of  the  bottles  was  broken  and  the  alcohol  had  escaped. 
I  therefore  left  all  of  the  material  with  Dr.  Eeeves,  requesting  him  to 
place  the  fragments  from  the  brolien  bottle  into  fresh  alcohol,  and  to 
hold  the  whole  subject  to  my  order. 

To  make  a  long  story  short,  Dr.  Eeeves  found  in  sections  from  one  of 
these  cases  bacilli  in  great  numbers,  which  were  photographed  for  him 
by  Dr.  Detmers,  of  OJiio.  The  sections  containing  those  bacilli  con- 
tained also  other  bacilli  and  micrococci.  The  bacillus  present  in  greatest 
abundance  resembles  in  its  morphology  my  bacillus  a,-,  it  certainly  is 
not  the  bacillus  of  Babes. 


Fig.  21.— Bacillus  of  Babes  in  kidney,  yellow  fever.    Material  from  Dr,  Lacerda'a  laboratory  in  Kio 

Janeiro. 

The  morphology  of  the  bacillus  of  Babes  and  its  distribution  in  the 
tissues  are  shown  in  Fig.  21,  which  is  taken  from  my  article  on  yellow 
fever  in  Wood's  Handbook  of  the  Medical  Sciences,  The  bacillus  is 
magnified  about  1,000  diameters,  while  the  amplification  for  the  tissue 
elements  is  450. 


180     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

Dr.  Babes'  drawings  of  the  same  bacillus  will  be  found  on  p.  525  of 
bis  work,  "  Les  Bacteries,"  Paris,  1886,  2d  edition. 

All  pathological  exports  to  whom  I  have  shown  a  duplicate  of  the  sec- 
tion from  which  Dr.  Detmers'  photographs  were  made  agree  with  me 
that  the  microorganisms  present  represent  a  post-mortem  invasion  of 
the  tissue,  and  of  the  particular  piece  of  tissue  from  which  the  section 
was  made.  The  outer  margin  of  the  piece  is  evidently  invaded  by 
putrefactive  organisms.  Whether  this  piece  came  from  the  broken 
bottle  I  can  not  say,  but  I  attach  no  importance  to  the  finding  of 
microorganisms  in  this  material  under  the  circumstances  mentioned, 
and  I  have  excluded  these  Decatur  cases  from  further  consideration, 
as  I  have  an  abundance  of  material  in  which  I  have  greater  confidence 
from  the  autopsies  made  in  Havana  in  1888  and  1889. 


VIII-DESCRIPTION  OF  MICROORGANISMS  ISOLATED  FROM 
YELLOAV-FEVER  CADAVERS,  AND  THE  ALVINE  DISCHARGES 
OF  THE  SICK. 

BACILLI. 
No.  1:  Bacterium  coli  commune  (Escherich).     My  bacillus  a. 

This  is  the  bacillus  which  I  have  obtained  most  frequently  in  my 
cultures  from  the  blood  and  tissues,  and  which  has  been  present  most 
constantly  and  abundantly  in  my  i)late  cultures  (Esmarch  roll-tubes)  in 
flesh-peptone-gelatine  from  material  obtained  post  mortem  from  the 
stomach  and  intestine,  and  from  the  alvine  discharges  of  the  sick. 
Being  a  facultative  anaerobic,  it  has  also  been  the  microorganism  most 
constantly  found  in  my  anaerobic  cultures  in  glycerine  agar. 

The  characters  of  this  bacillus  are  given  as  follows  in  a  paper  read 
by  the  writer  at  the  meeting  of  the  Association  of  American  Physicians 
held  in  Washington  in  September,  1888  : 

Bacillus  a  is  from  1^  to  4  times  as  long  as  broad,  and  has  a  diameter  of  about  0.6 
of  a  micromillinietre ;  the  dimensions  vary  considerably,  however,  in  diiferent  cul- 
tures, and  even  in  the  same  culture.  Under  certain  circumstances  the  ends  of  the 
rods  are  seen  to  be  more  deeply  stained  than  the  central  portion.  This  appearance 
is  not,  however,  constant,  and  seems  to  dej)end  upon  the  age  of  the  culture,  and  upon 
the  time  during  which  it  is  subjected  to  the  action  of  the  staining  reagent.  The  ends 
of  the  rods  are  more  or  less  rounded,  and  they  are  often  associated  in  pairs. 

Young  colonies  in  gelatine  (Esmarch  tubes)  have  a  pale  straw  color  which  after- 
ward becomes  pale  brown  ;  they  are  spherical  and  homogeneous,  or  lobate.  Colonies 
which  come  to  the  surface  often  present  the  appearance  of  a  rosette,  or  of  a  flower 
with  its  petals  expanded,  as  in  the  daisy.  From  cultures  in  which  lobate  colonies 
and  rosettes  were  the  prevailing  form  I  have  obtained  in  a  second  series  of  Esmarch 
tubes,  made  from  a  single  typical  rosette,  colonies  which  were  not  lobate,  and  which 
did  not  form  rosettes  (spherical  straw-colored  homogeneous  colonies);  and  in  these 
cultures  superficial  colonies  when  young  have  the  appearance  of  a  fragment  of  brolien 
glass;  later  they  present  an  irregular  margin,  and  a  more  or  less  wrinkled  appear- 
ance of  the  interior.  These  are  the  characters  of  the  bacillus  /  found  as  the  prevail- 
ing form  in  my  cultures  from  the  stomach  and  intestine  in  my  last  two  cases. 

It  is  a  very  curious  fact  that  during  the  last  week  of  my  stay  in  Havana  I  failed 
entirely  to  obtain  my  bacillus  a  in  lobate  colonies  and  rosettes,  although  I  have  three 
times  repeated  the  experiment  of  making  a  series  of  Esmarch  tubes  from  a  single 

181 


182     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

typical  colony  in  form  of  rosette  in  Esuiarcb  tubes  preserved  from  my  earlier  cases. 
In  every  instance  I  have  bad  instead  colonies  wbicb  are  identical  with  tbose  in  other 
Esmarcb  tubes  inoculated  at  the  same  time  from  single  colonies  of  my  bacillus/ of 
case  9  and  case  10.  As  the  morphology  of  the  bacilli  is  also  the  same  I  am  forced  to 
the  conclusion  that  bacillus  a  and  bacillus/ are  one  and  the  same,  and  that  the  char- 
acter M'hich  during  my  earlier  experiments  I  found  to  be  constant — i.  e.,  the  colonies 
in  form  of  a  rosette — is  not  so,  but  that  under  certain  circumstances,  at  present  un- 
determined, this  bacillus  forms  lobate  colonies  and  rosettes,  and  under  other  condi- 
tions homogeneous  spherical  colonies  in  the  deeper  portion  of  the  gelatine,  and  broken 
glass  colonies  upon  the  surface.  Later  these  colonies  have  an  irregular,  vitreous- 
looking  margin,  and  the  interior  has  a  brown  color,  more  or  less  intense. 

In  my  cultures  made  in  1889  the  bacterium  coli  commune  was  again 
the  bacillus  most  frequently  encountered,  but  the  rosette  colonies  found 
so  commonly  in  my  earlier  culture  experiments  in  1888  were  not  ob- 
served except  in  one  or  two  instances. 

My  identification  of  my  bacillus  a  with  the  hacterium  coli  commune 
of  Escherich  is  the  result  of  a  careful  study  of  cultures  in  various  media, 
made  side  by  side  with  it.  I  quote  again  from  my  paper  above  re- 
ferred to : 

Since  ray  return  to  Baltimore  I  have  given  much  time  ta  the  elucidation  of  the 
question  referred  to.  It  is  evident  that  if  identity  is  once  established  with  any 
known  bacillus  found  elsewhere  than  in  connection  with  yellow  fever,  the  micro- 
organism can  be  excluded  as  the  possible  specific  cause  of  this  disease.  But  the 
present  status  of  bacteriology  makes  it  also  evident  that  great  care  must  be  taken 
in  assuming  the  identity  of  microorganisms  from  different  sources,  and  that  morpho- 
logical characters  or  even  similarity  of  growth  in  culture  media  will  not  alone  suffice. 
Any  constant  difference  in.  physiological  characters,  as  for  example  in  pathogenic 
power  when  tested  on  various  animals,  must  be  accepted  as  establishing  a  specific 
form,  or  a  permanent  variety,  which  amounts  to  the  same  thing.  We  now  know,  for 
example,  two  spirilla  which  resemble  closely  the  spirillum  of  Asiatic  cholera  (the 
Finkler-Prior  spirillum  and  the  "cheese  spirillum"  of  Deneke),  but  which  have, 
nevertheless,  been  shown  by  carefully  conducted  experimsnts  to  be  different  in  certain 
particulars  which  would  easily  escape  notice  upon  a  superficial  comparison. 

I  have  felt  that  with  this  knowledge  to  guide  me  I  could  not  lightly  exclude  any 
microorganism  as  common,  and  especially  that  a  bacillus  which  was  so  prominent 
by  reason  of  its  constant  and  abundant  presence  should  receive  careful  consideration. 

Two  bacilli  have  been  described,  both,  of  which  are  found  in  the  intestines  of 
healthy  individuals,  which  in  their  morpholo  gy  resemble  my  bacillus  a,  found  in 
the  alimentary  canal  of  yelluw-fever  cases.  These  are  the  Bacillus  Neapolitanus  of 
Emmerich  and  the  Bacterium  coli  commune  of  Escherich.  Both  of  these  microorgan- 
isms have  been  the  object  of  extended  studies  by  German  bacteriologists,  and 
especially  the  bacillus  of  Emmerich,  on  account  of  his  claim  that  it  is  the  specific 
etiological  agent  in  the  disease  with  which  he  found  it  associated.  This  claim  has 
not  been  substantiated  j  on  the  other  hand,  it  has  been  shown  by  Weisser  *  that  "  in 
human  feces,  normal  as  well  as  abnormal,  in  the  air  and  in  putrid  material,  bac- 
teria are  found,  which  in  their  morphology,  their  biological  functions,  and  their 
pathogenic  action  upon  animals  are  identical  with  the  so-called  Naples  cholera- 
bacterium  of  Emmerich." 

I  have  had  for  comparison  a  culture  of  the  Emmerich  bacillus,  originally  from  one 
of  the  bacteriological  laboratories  of  Germany,  preserved  in  the  collection  main- 

*  Ueber  die  Emmerich'schen  sogenannten  Neapler  Cholerabacterien.  Zeitschrift  fiir 
Hygiene,  Band  1. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  183 

tained  under  the  direction  of  Prof.  William  II.  Welch  in  tlie  pathological  laboratory 
of  Johns  Hopkins  University.  For  a  culture  of  the  bacterium  coli  commune  I  am 
indebted  to  Dr.  William  D.  Booker,  of  Baltimore,  Avho  had  it  directly  from  Escber- 
ich.  The  characters  of  both  of  these  microorganisms  have  been  carefully  deiined; 
but  I  find  no  account  of  the  lobate  colonies  (deep),  or  of  the  superficial  colonies  in 
the  form  of  rosettes,  which  became  for  me,  during  my  earlier  experiments  in  Havana, 
the  diagnostic  character  bj^  which  I  recognized  my  bacillus  a  in  gelatine  Esmarch 
tubes.  By  lobate  colonies,  I  mean  that  instead  of  being  spherical  and  homogenous, 
the  colonies  are  divided  into  a  small  number  of  distinct  masses  without  losing  their 
spherical  outline.  In  some  cases  this  apparent  segmentation  of  the  colonies  ex- 
tended further,  and  they  becaiue  coarsely  granular  in  appearance.  The  superficial 
colonies  in  the  form  of  rosettes  also  varied  considerably,  the  margins  being  sometimes 
made  up  of  symmetrical  lobes,  shaped  like  the  petals  of  a  daisy — marguerite — and  at 
others  being  more  deeply  cleft  and  dentate.  If  this  character  of  growth  had  proved  to 
be  constant  it  would  iiufiice  to  differentiate  my  bacillus  a  from  the  two  microorganisms 
in  question.  But  it  proves  not  to  be  constant,  and  since  my  return  to  Baltimore  I 
have  only  obtained  these  rosette  colonies  exceptionally,  and  have  not  been  able  to 
determine  the  precise  conditions  which  determine  their  formation.  But  I  have 
ascertained  that,  cultivated  side  by  side  in  the  same  media  and  under  the  same  con- 
ditions of  teuiperature,  the  colonies  formed  in  gelatine  Esmarch  tubes  are  identical 
in  the  case  of  my  bacillus  a,  and  the  colon  bacillus  of  Escherich.  The  growth  upon 
agar-agar  and  uiion  potato  is  also  identical,  and  the  reducing  power  upon  litmus 
added  to  sterilized  milk. 

My  gelatiue  cultures  have  been  made  in  flesh-peptone  gelatine  containing  20  per 
cent,  of  gelatine,  instead  of  10  per  cent,  as  in  Koch's  original  formula.  I  have  found 
this  to  stand  the  summer  heat  of  Baltimore  without  liquefaction,  and  during  the 
months  of  May  and  June  used  it  with  great  satisfaction  in  Havana  for  Esmarch 
tubes  and  stick  cultures.  It  will  stand  a  temperature  of  about  6d°  F.  (30°  C),  and 
so  far  as  I  can  see  answers  as  a  culture  medium  for  diagnostic  purposes  quite  as  well 
as  that  containing  10  per  cent,  of  gelatiue. 

The  idea  which  I  had  entertained  that  isolated  colonies  in  Esmarch  tubes  should 
give  me  pure  cultures  of  a  single  organism  has  proved  not  to  be  true  in  many  instances 
in  my  first  series  of  tubes  inoculated  with  material  from  the  intestine  or  stomach, 
and  it  seems  probable  that  such  colonies  frequently  originate  from  little  masses  of 
associated  microorganisms,  rather  than  from  a  single  bacillus.  In  making  gelatine 
stick  cultures  in  20  per  cent,  gelatine  from  single  Esmarch  colonies  of  my  bacillus  a, 
I  ha've  frequently  had,  both  in  Havana  and  since  my  return  to  Baltimore,  an  out- 
growth at  intervals  along  the  line  of  puncture,  which  is  shown  in  Fig.  1  of  the  plate 
accompanying  this  paper  (Plate  V).  This  consists  of  feathery  tufts  growing  out  into 
the  gelatiue.  To  test  the*  question  whether  these  tufts  represent  a  different  microor- 
ganism or  a  different  mode  of  growth  of  the  same,  I  have  several  times  carefully 
broken  the  test  tube  containing  a  growth  like  that  shown  in  Fig.  2,  and  have  made 
a  stick  culture  in  gelatine  from  the  feathery  tuft  and  also  from  that  part  of  the  stick 
which  was  free  from  these  outgrowths;  one  from  the  tuft  has  been  a  similar  growth 
all  along  the  line  of  puncture,  as  shown  in  Fig.  3;  the  other  has  resembled  pre- 
cisely that  portion  of  the  original  stick  culture  which  was  free  from  these  outgrowths. 
Having,  in  Havana,  made  this  differentiation,  I  designated  the  tufted  growth  bacil- 
lus I.  The  morphology  of  the  bacillus  when  cultivated  in  bouillon  or  obtained  from 
the  surface  of  an  agar  or  gelatine  culture  appeared  to  be  identical  with  that  of  ba- 
cillus a;  but  preparations  mounted  directly  from  the  feathery  tufts  showed  that, 
together  with  short  oval  bacilli  of  the  typical  form,  there  were  numerous  long 
filaments  like  that  shown  at  a,  in  Fig.  6.  A  very  curious  thing  about  my  stick 
cultures  of  this  bacillus  ?,  made  in  Havana,  was  that  after  a  few  days  they  assumed 
a  brownish  color,  which  in  time  became  black. 


184     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

In  cultivatiug  Emniericli's  bacillus  in  20  per  cent,  gelatine  at  a  temperature  of  28° 
to  30^  C.  (82.4°  to  86^  F.)  I  have  obtained  tbe  same  radiating  feathery  growth  as  is 
presented  by  m^"  bacillus  Z.  This  is  shown  in  Fig.  4,  which,  like  the  other  figures 
illustrating  this  paper,  is  copied  from  a  photograph  made  by  myself.  This  mode  of 
growth,  so  far  as  I  know,  has  not  been  described,  but  I  have  no  reason  to  doubt  the 
authenticity  of  the  stock  from  which  the  culture  was  made.  The  growth  upon  potato 
aud  the  morphology  correspond  with  the  descriptions  of  those  who  have  specially 
studied  this  bacillus,  and  with  my  bacillus  ?.  I  am  therefore  forced  to  the  conclusion 
that  they  are  identical.  The  morphological  characters  of  this  bacillus  are  shown  in 
Fig.  6,  which  is  made  from  a  bouillon  culture  of  bacillus  I,  separated,  as  heretofore 
stated,  while  in  Havana,  from  a  stick  culture  of  my  bacillus  a  {Bacterium  coU  commune 
of  Escherich). 

I  must  now  call  attention  to  Fig.  5.  This  is  from  a  stick  culture  in  20  per  cent, 
gelatine  of  the  colon  bacillus  of  Escherich,  obtained  from  him,  as  heretofore  stated, 
through  Dr.  Booker,  of  Baltimore.  AVe  haTehere  a  feathery  outgrowth  along  the  line 
of  puncture,  which  appears  to  be  identical  with  that  shown  in  Fig.  Ifrom  my  bacillus  a. 
To  test  the  question  of  identity  I  broke  this  tube  and  made  a  stick  culture  in  20  per 
cent,  gelatine  from  the  tuft  at  a,  and  another  from  the  clear  portion  of  the  column 
above  this  point.  The  result  was  a  growth  in  the  first  tube  like  that  from  which  the 
inoculation  was  made,  similar  to  Figs.  3  and  4,  and  in  the  second  tube  the  charac- 
teristic growth  of  the  colon  bacillus,  viz,  spherical,  light  brown  colonies  crowded 
together  into  a  central  core  at  the  upper  part  of  the  puncture,  but  more  or  less  dis- 
tinct and  separate  at  the  lower  extremity.  Thus  it  will  be  seen  I  have  had  the  same 
result  from  this  authentic  culture  of  the  colon  bacillus  which  was  sent  by  Escherich 
to  Dr.  Booker,  and  had  been  passed  through  a  series  of  Esmarch  tubes  by  the  last- 
named  bacteriologist,  as  that  obtained  in  Havana  and  since  in  Baltimore  from  stick 
cultures  of  my  bacillus  a.  This  forces  me  to  one  of  two  conclusions  :  Either  the  colon 
bacillus  of  Escherich  aud  the  bacillus  of  Emmerich  may  remain  associated  after  pass- 
ing a  culture  containing  them  through  a  succession  of  plate  cultures  (Esmarch  tubes) 
or  the  so-called  bacillus  of  Emmerich  (my  bacillus  I)  is  a  variety  of  the  colon  bacil- 
lus— a  sport  which  is  produced  under  certain  circumstances,  and  which  retains  its 
distinctive  character  for  a  certain  time.  I  am  not  prepared  at  present  to  decide  this 
question  in  a  definite  manner,  but  propose  to  keep  it  in  view  in  my  future  studies  of 
these  microorganisms. 

I  have  since  obtained  the  same  tufted  outgrowth  in  gelatine  stick 
cultures  from  single  Esmarch  colonies  of  my  bacillus  a  in  cultures  from 
feces  made  in  Decatur,  Ala.,  and  from  the  contents  of  the  stomach  and 
intestines  of  yellow-fever  cadavers,  made  in  Havana  in  1889.  Although 
not  constant,  this  outgrowth  is  so  common  in  my  stick  cultures  in 
20  per  cent,  gelatine  that  1  have  come  to  look  upon  it  as  one  of  the 
distinguishing  characters  of  the  colon  bacillus. 

Fliigge  speaks  of  this  bacillus  as  having  '■'■(jeringe  BeicegliehJceit,''^  and 
Eisenberg  in  his  Bakteriologische  Diagnostik,  says :  "  Triige  beweglich." 
I  have  never  been  able  to  convince  myself  that  the  colon  bacillus,  either 
in  my  cultures  from  yellow-fever  cadavers,  etc.,  or  from  Escherich's 
stock,  obtained  by  me  from  Dr.  Booker,  has  any  proper  vital  move- 
ments. I  have  observed  in  hanging  drop  cultures  motion  in  situ,  which 
I  take  to  be  molecular,  although  it  is  not  as  active  as  the  molecular 
movements  of  inorganic  particles  are  often  observed  to  be.  It  is  rather 
a  gentle  swinging  motion  of  the  little  rods  in  the  direction  of  their 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER.  185 

long  axis,  and  is  not  attended  with  a  change  of  location  of  individual 
rods  with  reference  to  others  in  the  same  field. 

While  iu  Havana  and  since  my  return  to  Baltimore  I  have  made  numerous  inocu- 
lation experiments  in  rabbits  and  guinea  pigs,  with  cultures  of  this  bacillus.  The 
general  results  obtaiued  may  be  briefly  stated  as  follows : 

The  injection  iuto  the  cavity  of  the  abdomen  of  a  considerable  quantity  of  a  bouil- 
lon culture,  for  a  full  grown  rabbit  from  3  to  5  cubic  centimetres,  causes  a  decided 
elevation  of  temperature,  which  may  amount  to  more  than  '2°  C.  (3.6°  F.),  and  death 
usually  occurs  within  2  to  4  days.  A  certain  proportion  of  the  animals,  however,  sur- 
vive these  large  doses,  and  in  smaller  amounts  (less  than  2  cubic  centimetres)  recovery 
is  the  rule.  That  the  febrile  movement  is  due  to  a  ptomaine  produced  during  the  active 
development  of  the  microorganism  is  indicated  by  the  fact  that  cultures  sterilized  by 
heat  (70°  C,  158=  F. )  for  10  minutes  likewise  give  rise  to  a  temporary  rise  of  tem- 
perature. 

In  fatal  cases  in  which  nonsterilized  cultures  were  injected  into  the  cavity  of  the 
abdomen,  I  have  recovered  the  bacillus  from  the  blood  and  tissues,  in  pure  cultures, 
and  these  possess  pathogenic  properties  identical  with  those  shown  by  the  original 
cultures. 

The  number  of  bacilli  present  in  the  blood  and  liver  is  comparatively  small,  as  is 
shown  by  the  examination  of  stained  smear  preparations. 

The  most  striking  post-mortem  appearance  in  animals  which  succumb  to  an  intra- 
peritoneal injection  is  a  rosy  hypeia^mia  of  the  small  intestine.  The  liver  is  dark  in 
color,  full  of  blood,  and  rather  soft.     The  spleen  is  normal  in  appearance. 

These  results  show  that  in  its  pathogenic  properties,  as  well  as  in  its  morphology 
and  growth  in  culture  media,  my  bacillus  a  corresponds  Avith  the  bacterium  coli 
commune  of  Escherich,  and  consequently  that  it  is  not  the  specific  etiological  agent 
in  yellow-fever. 

The  following  is  a  partial  record  of  experiments  made : 

May  15, 1838,  1  p.  m. — Injected  into  cavity  of  abdomen  of  rabbit  No.  2,  one-half 
cubic  centimetre  bouillon  culture  of  bacillus  a.     Result  negative. 

May  1.''),  1:30^.  ??i..— Injected  iuto  cavity  of  abdomen  of  rabbit  No.  3,  2  cubic  centi- 
metres bouillon  culture  bacillus  a  ;  3:20  p.  m.,  temperature  104.5°  ;  May  16,  7  a.  m., 
temperature  106°  ;  3  p.  m.,  104.5°;  May  20,  apparently  well;  injected  into  cavity  of 
abdomen  3  cubic  centimetres  bouillon  culture  bacillus  a.  Found  dead  at  6  a.  m.. 
May  24. 

^ay  15,  1  j;.  m. — Injected  into  cavity  of  abdomen  of  rabbit  No.  4,  2  cubic  centi- 
metres bouillon  culture  of  bacillus  a.  Temperature  at  3:30  ]>.  m.,  104°  ;  May  16,  at  7 
a.  m.,  temperature  105.5°  ;  3  p.  m.,  104.5°;  May  17,  7  a.  m.,  appears  better.  May  21, 
7  a.  m.,  found  dead. 

May  20. — Injected  into  cavity  of  abdomen  of  rabbit  No.  5,  2  cubic  centimetres 
bouillon  culture  bacillus  a;  found  dead  on  the  morning  of  May  25. 

May  18,  12:30  j;.  m.— Injected  into  cavity  of  abdomen  of  rabbit  No.  7,  15  cubic  centi- 
metres sterilized  bouillon  culture  of  bacillus  a  (sterilized  by  heat  at  160°  F.).  Tem- 
perature at4p.  m.,40.9°  C;  at  8  p.m., 40.4°  C;  May  19,  6  a.  m.,  temperature  39.6°  C; 
12m.,  39.4°;  4  p.  m.,  39.8°  ;  20,  6  a.  m.,  temperature  39.5°  C.  At  12  m..  May  20,  in- 
jected subcutaueously  2  cubic  centimetres  bouilliou  culture  of  bacillus  a  and  the  same 
amount  into  the  cavity  of  the  abdomen — to  test  protection  by  sterilized  culture. 
May  21,  6  a.  m.,  temperature  39.2°  ;  found  dead  on  the  morning  of  May  25. 

May  18,  12:30  jj.  m. — Injected  subcutaueously  into  rabbit  No.  8,  5  cubic  centimetres 
sterile  culture  of  bacillus  a  ;  temperature  just  before  injection  39.6°;  temperature  at 
4  p.  m.,  40.6°.  Second  injection  of  5  cubic  centimetres  sterile  culture  made  at  4  p.  m., 
temperature  at  8  p.  m.  40.7°.     May  19,  6  a.  m.,  temperature  41°,  gave  a  third  dose  of 


186  ETIOLOGY    AND    PREVENTION    OF   YELLOW    FEVES. 

3  cubic  centimeters  sterile  culture ;  12  m.,  temperature  40°,  injeclecl  a  fourth  dose  of 
3  cubic  centimeters  sterile  culture;  4  p.  m.,  temperature 41.1°,  injected  3  cubic  centi- 
meters sterile  culture;  8  p.  m.,  temperature  41. 6*^,  injected  3  cubic  centimeters  ster- 
ile culture.  May  20,  6  a.  m.,  temperature  40.5°,  injected  5  cubic  centimetres  sterile 
culture;  12  m.,  temperature  39.2°.  Died  at  4  p.  m.  May  21,  liver  large  and  rather 
soft;  spleen,  normal;  intestine,  normal. 

May  22,  12  m. — Injected  into  a  small  rabbit.  No.  9,  2  cubic  centimetres  mixed  bouil- 
lon and  agar  cultures,  bacillus  a  ;  result,  negative. 

May  22,  12  m. — Injected  into  a  small  rabbit.  No.  10,  2  cubic  centimetres  of  a  mixed 
bouillon  and  agar  culture,  bacillus  a  ;  found  dead  next  morning. 

May  31. — Injected  into  cavity  of  abdomen  of  rabbit  No.  13,  3  cubic  centimetres 
bouillon  culture  of  bacillus  a;  found  dead  at  6  a.  m.  June  2;  liver  dark  in  color  and 
rather  soft,  stomach  and  intestine  normaL 

July  26,  1889,  7  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  No.  128,  4  cubic 
centimetres  culture  in  agua  coco  of  bacillus  a  from  yellow  fever  feces  No.  3.  July  27, 
3  p.  m.,  the  animal  is  quite  feeble;  28,  6  a.  m,,  found  dead;  peritonitis. 

May  13,  6:15j>.  to. — Injected  subcutaneously  into  guinea-pig  No.  1,  2  cubic  centi- 
meters bouillon  culture  bacillus  a.  May  14,  7  a.  m.,  appears  sick  and  declines  food; 
May  15,  appears  better ;  May  16,  eats  a  little  ;  May  17,  appears  dull ;  May  18,  died  at  8 
a.  m.  Liver  appears  to  be  of  a  lighter  color  than  usual  (fatty  ?);  bladder,  empty ;  stom- 
ach, empty;  large  intestine  filled  with  a  dark  liquid,  bloody,  resembling  that  some- 
times found  in  intestine  of  yellow  fever  cadavers  ;  reaction  slightly  acid.  Bacillus  a 
recovered  in  cultures  from  blood  of  heart  and  from  liver. 

May  18,  12  m. — Injected  subcutaneously  into  guinea-pig  No.  2,  2  cubic  centimetres 
bouillon  culture  bacillus  a;  4  p.  m.,  temperature  39.2°;  8  p.  m.,-38.7°.  May 
19,  G  a.  m.,  temperature  38.7°,  animal  appears  sick;  12  m.,  temperature  39.5°;  4  p. 
m.,  tomperature  39.2°.  May  20,  6  a.  m.,  temperature  38.4°  ;  12  m.,  38.3°.  May  21, 
12  m.  38.7°.  May  22,  6  a.  m.,  temperature  38.2°  ;  animal  appeared  well  and  was 
used  for  another  experiment. 

May  18,  12  m. — Injected  into  guinea-pig  No.  3,  10  cubic  centimetres  sterQized  cul- 
ture of  bacillus  a  ;  5  cubic  centimetres  in  cavity  of  abdomen,  and  5  cubic  centimetres 
subcutaneously.  Temperature  in  rectum  immediately  after  injection  39.2°  C;  4  p. 
m.,  38.2°;  8  p.  m.,  38.3°;  May  19,  6  a.  m.,  temperature  38.6°;  12  m.,  38.6°;  4:30  p. 
m.  39.4°;  May  20,  6  a.  m.,  temperature  39.8°;  12  m.,  39.2°  ;  May  21,  12  m.,  38.8°; 
May  22,  remains  well. 

May  18,  12  m. — Injected  into  cavitj'  of  abdomen  of  guinea-pig  No.  4,  one-half  a 
cubic  centimetre  bouillon  culture  bacillus  a.  Temperature  immediately  after  injec- 
cion  39.6°;  4  p.  m.,  temperature  40.5°;  8  p.  m.,  39.6°  ;  May  19,  6  a.  m.,  temperature 
38.6°  ;  12  m.,  39.3°;  May  20,  6  a.  m.,  temperature  39.5°  ;  May  21,  12  m.,  temperature 
38.9°  ;  the  animal  rem  ined  in  good  health. 

Upon  my  return  from  Havana,  in  1888,  I  was  still  uncertain  whether 
the  little  tufts  developed  along  the  line  of  puncture  in  gelatine  stick 
cultures  of  my  bacilhis  a  were  to  be  considered  a  "  wuchsform"  of  this 
bacillus,  or  an  associated  bacillus  which  was  specifically  distinct.  As 
already  stated  I  made  cultures  from  these  tufts  by  breaking  the  test- 
tube,  and  designated  this  bacillus  I.  The  following  experiments  upon 
animals  have  been  made  with  pure  cultures  of  the  bacillus  obtained  in 
this  way : 

Baltimore,  Julyi'y,  1838. — Injected  subcutaneously  into  rabbit  No.  25,  4  cubic  centi- 
metres bouiUon  culture  of  bacillus  I.     Result  negative. 

Baltimore,  September  1,  1888. — Injected  subcutaneously  into  rabbit  No.  33,  15  cubic 
centimetres  sterilized  bouillon  culture  bacillus  I.     Result  negative. 


ETIOLOGY    AND    PREVENTiON    OF    YELLOW    FEVER.  187 

Baltimore  July  10,  1888.— Injected  into  cavity  of  abdomen  of  guinea-pig  No.  8,  1, 
cubic  centimetre  l)ouillon  culture  of  bacillus  I.  July  12,  3  p.  m.,  the  animal  was  very 
sick  and  was  killed.  Peritonitis;  small  intestine  hj'peraemic  ;  liver  dark  in  color; 
spleen  slightly  enlarged. 

Baltimore,  July  lU,  1888.— Injected  into  cavity  of  abdomen  of  guinea-pig  No.  9,  4 
cubic  centimetres  bouillon  cultures  of  bacillus  I.  Anin)al  found  dead  morning  of 
July  13.  Small  intestine  hyperfemic  ;  liver  dark  in  color  ;  gall  bladder  distended 
with  a  clear  fluid. 

Baltimore,  July  16,  18S8. — Injected  subcutaneously  into  guinea-pig  No.  10,  one-half 
cubic  a  centimetre  bouillon  culture  bacillus  I.     Result  negative. 

Baltimore,  July  16,  1888. — Injected  subcutaneously  into  guinea-pig  No.  11,  2  cubic 
centimetres  bouillon  culture  bacillus  I.     Result  negaiive. 

Baltimore,  July  16,  1888. — Injected  into  cavity  of  abdomen  of  guinea-pig  No.  12, 
one-half  a  pubic  centimetre  bouillon  culture,  bacillus  I.     Result  negative. 

Baltimore,  July  16,  1888. — Injected  into  cavity  of  abdomen  of  guinea-pig  No.  13, 
one-half  a  cubic  centimetre  bouillon  culture,  bacillus  I.     Result  negative. 

Baltimore,  July  21,  1888. — Injected  into  lumen  of  intestine  of  small  black  dog,  3 
cubic  centimetres  bouillon  culture  bacillus  I.     Result  negative. 

Baltimore,  July  21,  1888.— Injected  into  Ir.men  of  intestine  of  large  dog,  4  cubic 
centimetres  bouillon  culture  bacillus  I.    Result  negative. 

These  experiments  will  suffice  to  show  that  this  bacillus  does  not 
produce,  in  the  animals  experimented  upon,  any  symptoms  or  patho- 
logical changes  which  can  be  identified  with  those  of  yellow  fever  in 
man. 

NO.  2.  BACILLUS  x  (HAVANA,  1889.) 

The  general  results  of  my  culture  experiments  in  1888  having  enabled 
me  to  exclude  the  supposition  that  the  specific  infectious  agentin  the  dis- 
ease under  investigation  is  a  liquefying  microorganism,  I  have  naturally 
turned  my  attention  to  the  nonliquefying  bacilli  present  in  the  alimen- 
tary canal,  and  in  certain  cases  obtained  in  my  cultures  from  the  tissues. 
The  one  most  constantly  and  abundantly  present,  my  bacillus  a,  having 
been  excluded,  I  have  given  much  time  to  the  study  of  other  non- 
liquefying  bacilli  associated  with  it,  and  especially  to  that  one  which  I 
have  designated  by  the  letter  oc,  and  which,  for  the  present,  1  shall  give 
no  other  name. 

This  bacillus  resembles  the  hacterium  coli  commune  (bacillus  a)  in  its 
morphology,  although  somewhat  larger;  and  its  colonies  in  gelatine 
roll-tubes  are  also  quite  similar,  especially  when  young.  It  is,  how- 
ever, fully  differentiated  from  the  "colon  bacillus"  by  its  pathogenic 
power  when  injected  into  the  peritoneal  cavity  of  rabbits. 

I  am  now  satisfied  that  this  bacillus  was  present  in  my  cultures  made 
from  the  intestine  of  yellow-fever  cadavers  in  1888,  although  I  did  not 
differentiate  it  from  my  bacillus  a  at  that  time.  This  is  shown  by  the 
pathogenic  potency  of  certain  cultures  supposed  to  contain  only  bacil- 
lus a,  while  pure  cultures  in  bouillon,  made  from  single  colonies,  proved 
not  to  be  pathogenic.  The  apparently  contradictory  results  obtained 
in  mj' inoculation  experiments  I  could  not  at  the  time  explain,  but  now 
believe  this  to  be  the  true  explanation.     I  first  recognized  this  bacillus 


188     ETIOLOGY  AXD  PREVENTION  OF  YELLOW  FEVER. 

by  its  pathogenic  i)Ower,  iu  experiments  starting  from  material  ob- 
tained from  the  liver  of  case  18  (autoi)sy  May  13, 1889).  Three  minims 
of  this  material,  containing  also  the  large  anaerobic  bacillns  designated 
by  the  letter  X  in  my  experiments  made  at  this  date,  was  injected  into 
guinea  pig  ]S'o.  43.  Death  occurred  at  the  end  of  11  hours.  A  second 
guinea  pig  (Xo.  45)  was  inoculated  with  3  minims  of  bloody  serum  from 
the  subcutaneous  connective  tissue  of  the  first.  At  the  end  of  48  hours 
there  was  a  pouch  in  the  abdominal  walls  containing  a  collection  of 
bloody  serum.  A  little  of  this  was  drawn  off  in  a  capillary  tube,  and 
cultures  made  from  it.  It  was  in  these  cultures  that  I  first  recognized 
my  bacillus  .r.  Its  great  pathogenic  power  when  injected  into  the 
cavity  of  the  abdomen  of  rabbits  was  first  demonstrated  by  the  follow- 
ing experiment: 

Havana,  May  22,  12  m.,  1889. — Injected  into  tlie  cavity  of  the  abdomen  of  rabbit 
No.  108,  1  cubic  centimetre  culture  of  bacillus  x  iu  glycerine  agar.  At  2:30  p.  m.  tbe 
animal  is  lying  upon  its  side  breathing  slowly,  and  is  evidently  dying;  died  at 
2:40  p.  m. 

Other  experiments,  showing  the  virulence  of  cultures  of  this  bacillus, 
will  be  given  later.  My  object  at  present  is  to  i)oint  out  the  fact  that 
it  is  differentiated  from  bacillus  a  by  this  x)athogenic  power. 

In  my  subsequent  researches  I  have  obtained  this  bacillus  iu  about 
one-half  the  cases,  either  directly  in  my  cultures  from  material  con- 
tained in  the  small  intestine,  or  indirectly  in  my  inoculation  experi- 
ments upon  rabbits  and  guinea  pigs.  It  does  not  follow  that  it  was 
not  present  in  those  cases  in  which  I  have  not  demonstrated  its  pres- 
ence. My  autopsies  at  this  time  followed  each  other  in  quick  succes- 
sion, and  a  complete  bacteriological  study  of  each  case  was  impracti- 
cable. If  the  colonies  in  gelatine  roll-tubes  had  i^resented  well-marked 
differences  from  those  of  the  colon  bacillus,  the  matter  would  have  been 
greatly  simplified;  but  I  did  not  feel  justified  in  attempting  to  decide 
that  bacillus  x  was  present  in  such  tubes  from  an  examination  of  the 
colonies  alone,  or  from  this  and  the  examination  of  a  stained  prepara- 
tion together.  ]S"othing  short  of  the  inoculation  of  a  pure  culture  into 
the  cavity  of  the  abdomen  of  a  rabbit  seemed  to  me  at  that  time  to 
suffice  for  the  differentiation.  The  difficulty  is  increased  by  the  fact  that 
the  colonies  of  both  bacilli  vary  considerably  in  the  same  medium  at 
different  times.  In  general,  however,  the  deep  colonies  of  bacillus  co 
are  more  opaque,  and  of  a  deeper  brown  color  than  those  of  the  colon 
bacillus,  and  the  superficial  colonies  are  thicker  and  more  opaque.  The 
difficulties  referred  to  prevent  me  also  from  estimating  with  any  degree 
of  accuracy  the  relative  abundance  of  bacillus  x  in  the  contents  of  the 
intestine.  I  do  not  hesitate  to  say,  however,  that  the  colon  bacillus 
has  been  the  most  constant  and  most  abundant  microorganism  in  my 
cultures  from  this  source.  I  have  more  frequently  obtained  bacillus  x 
in  my  inoculation  experiments  than  in  cultures  made  directly  from  the 
contents  of  the  intestine  or  material  from  the  liver  kept  in  an  anti- 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  189 

septic  wrapping.     It  has  been  frequently  present  in  cultures  made  from 
the  liver  of  animals  which  have  died  from  such  inoculations. 

CHARACTERS   OF   BACILLUS  X. 

This  bacillus  varies  considerably  in  its  morphology,  as  is  shown  by 
my  photomicrographs.  In  recent  gelatine  cultures  it  is  often  so  shorty 
an  oval  in  form  that  it  might  be  mistaken  for  a  micrococcus.  In  cul- 
tures in  bouillon  or  in  cocoanut  water  it  resembles  the  colon  bacilluSj 
but  is  larger — Iju  or  more  in  diameter.  The  rods  are  often  united  in 
pairs,  and  in  the  same  culture  may  vary  considerably  in  length  (Fig.  3, 
PI.  VI).  In  potato  cultures  they  are  seldom  seen  as  long  as  in  Fig.  2, 
PI.  VI,  which  is  exceptional  in  this  regard,  and  led  to  the  suspicion  that 
another  bacillus  had,  by  accident,  taken  possession  of  the  sterilized 
X)otato  on  which  bacillus  x  had  been  planted.  But  upon  making  gela- 
tine roll  tubes  from  this  culture  it  proved  to  be  a  pure  culture  of  bacil- 
lus Xj  and  upon  replanting  it  on  another  potato  presented  its  usual 
form.  In  my  j)hotomicrograph  from  this  potato  culture  it  will  be  observed 
that  some  of  the  rods  present  the  appearance  of  not  being  filled  out  at 
the  ends,  and  others  show  a  faint  line  at  the  extremity,  which  seems  to 
include  a  vacuole,  or  unstained  extremity  of  the  rod.  This  is  an  ap- 
pearance which  I  have  frequently  noticed  not  only  in  potato  cultures, 
but  in  those  in  various  liquid  media.  When  stained  preparations  are 
examined  with  the  full  light  of  the  Abbe  condenser,  the  ends  of  some 
of  the  rods  appear  to  be  cut  away,  leaving  a  concave  extremity;  but 
by  using  a  small  diaphragm  to  obtain  definition  it  will  be  seen  that  the 
cell  wall  extends  beyond  the  stained  portion  of  the  rod  and  includes 
what  appears  to  be  a  vacuole.  There  is  no  reason  to  believe  that  this 
appearance  is  due  to  the  presence  of  an  end  spore,  for  the  supposed 
vacuole  is  not  refractive,  as  a.  spore  would  be,  and  my  experiments  on 
the  thermal  death  point  of  this  bacillus  indicate  that  it  does  not  form 
spores.  Cultures  are  sterilized  by  exposure  for  10  minutes  to  a  tem- 
perature 160O  F.  (71.2°  C). 

A  very  curious  thing,  with  reference  to  this  bacillus,  is  that  it  pre- 
sented active  movements  in  mj^  cultures  made  directly  from  yellow- 
fever  cadavers,  but  that  these  movements  were  not  constant,  and  that 
since  my  return  to  Baltimore  I  have  not,  as  a  rule,  observed  active 
movements  in  cultures  from  the  same  stock,  which,  however,  preserved 
their  pathogenic  power  and  other  characters.  In  Havana  these  move- 
ments were  usually  not  observed  in  all  the  bacilli  in  a  field  under  ob- 
servation, but  one  and  another  would  start  from  a  quiescent  condition 
on  an  active  and  erratic  course  ;  sometimes  spinning  actively  upon  its 
axis, and  again  shooting  across  the  field  as  if  propelled  by  a  flagellum. 

My  notes  indicate  that  cultures  passed  through  the  guinea-pig  are 
more  apt  to  be  motile,  but  my  attention  had  not  been  called  to  this 
until  now  that  I  am  engaged  in  writing  them  out.  Thus  I  find  recorded 
in  my  Havana  notes  "Single  colonies  from  guinea-pig  Ko,  136  the, 


190     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

bacillus  is  actively  motile ;  also  from  gelatine  stick  culture  of  2  days 
made  from  single  colony;  also  motile  in  cultures  in  cocoanut  water  at 
times ;  at  otber  times  not.  The  movements  are  rapidly  progressive  or 
rotatory." 

This  culture  from  guinea-pig  No.  136  was  one  of  the  stock  cultures 
which  1  brought  home  with  me,  and  which  has  served  for  my  experi- 
ments in  Baltimore.  It  came  through  a  series  of  inoculated  guinea 
pigs  from  the  liver  of  case  28,  as  follows  : 

Havana,  July  16,  7:30  a.  m.,  1889. — Injected  subcutaneously  into  guinea-pig  153 
5  minims  blood  and  crushed  parenchyma  from  liver  of  case  28  *  containing  bacillus 
N.,  etc.  At  12  m.  the  animal  is  running  about  the  cage  in  the  usual  restless  and 
eccentric  manner.  Died  at  10  p.  m.  Extensive  ei3Pi»sion  of  bloody  serum,  with  sepa- 
ration of  the  skin  over  abdominal  walls  ;  various  bacilli  in  this  bloody  serum. 

July  17,  8  a.  m. — Injected  subcutaneously  iuto  guinea-pig  154  5  minims  of  bloody 
serum  from  cellular  tissue  of  guinea-pig  153.  Convulsions  at  8:30  a.  m.,  July  18. 
Died  at  12:30.  Extensive  subcutaneous  oedema  and  softening  of  tissues.  Liver 
rather  dark  in  color,  spleen  somewhat  enlarged.  Culture  from  liver  large  motion- 
less bacillus  (n),  and  smaller  motile  bacillus  (x), 

July  18,  5p.  m. — Injected  into  guinea-pig  157  4  minims  of  bloody  serum  from  con- 
nective tissue  of  guinea-pig  154.  July  20  :  The  animal  has  an  extensive  collection 
of  bloody  serum  in  the  walls  of  the  abdomen  (some  of  this  was  drawn  off  aud  in- 
jected into  guinea-pig  160,  which  died  at  end  of  20  hours).  July  21 :  The  animal  has 
been  very  sick,  but  seems  better.  Killed  at  5  p.  m.,  July  21;  liver  dark  in  color, 
abdominal  viscera  normal. 

July  20,  7:30  a.  m. — Injected  subcutaneously  4  minims  of  bloody  serum  drawn  dur- 
ing life,  from  subcutaneous  connective  tissue  of  guinea  pig  No.  157  into  guinea  pig 
No.  160.  Died  at  12:30,  July  21.  No  subcutaneous  osdema,  librinous  deposit  ou 
surface  of  liver,  which  is  rather  light  iu  color,  stomach  hyperaemic.  Obtained  bacil- 
lus X  in  cultures  from  liver. 

It  is  from  this  source,  and  from  another  series,  started  from  case  18, 
that  my  experiments  with  bacillus  x  have  been  made. 

Turning  now  to  my  Baltimore  notes  I  find:  "  Eecovered  bacillus  ic 
from  spleen  and  liver  of  guinea-pig  190,  and  spleen  of  189.  In  this 
culture  in  cocoanut  water,  at  the  end  of  24  hours,  bacillus  x  is  actively 
motile,  as  in  my  first  cultures  in  Havana." 

These  two  guinea  pigs  received,  by  subcutaneous  injection,  on  the 
17th  of  December,  1889,  1  cubic  centimeter  of  a  culture  of  bacillus  x 
in  cocoanut  water,  one  week  old.  The  experiment  was  made  to  see  if 
bacillus  X  could  be  recovered  after  an  interval  of  several  days.  The 
animals  remained  in  apparent  good  health  (bacillus  x  alone  does  not 
kill  guinea  pigs  when  injected  subcutaneously).  On  the  23d  of  Decem- 
ber the  animals  were  killed  and  cultures  made,  with  the  usual  precau- 
tions, from  their  liver  and  spleen. 

All  of  these  contained  bacillus  x  in  pure  cultures,  and  actively  motile, 
as  in  Havana.  With  this  exception  I  have  not  observed  active  move- 
ments in  my  numerous  cultures  of  this  bacillus  since  my  return  to 
Baltimore.     That  it  was  the  veritable  x  which  I  recovered  from  the 

*  This  is  a  case  in  which  the  autopsy  w^as  made  9  hours  after  death^  and  smear  prep- 
arations from  the  liver  showed  the  presence  of  bacilli. 


ETIOLOGY    AND    PREVENTION    OF   YELLOW    FE'^ER.  191 

above-mentioned  guinea-pigs  was  demonstrated  by  making  cultures  in 
gelatine  roll  tubes,  etc. 

In  gelatine  stick  cultures  the  growth  of  bacillus  x  resembles  that  of 
the  colon  bacillus,  but  the  colonies  at  the  bottom  of  the  line  ot  punc- 
ture are  more  opaque  and  not  of  a  clear  amber  color  like  that  of  colonies 
of  the  colon  bacillus.  Upon  the  surface  the  growth  is  thicker  than  that 
of  the  colon  bacillus,  and  forms  a  milk  white,  soft  mass,  Fig.  7,  PI.  VI. 

The  tufted  outgrowth  observed  so  frequently  in  gelatine  stick  cul- 
tures of  my  bacillus  a  does  not  occur  in  similar  cultures  of  this  bacillus. 

This  bacillus  is  2b  facultative  anaerobic. 

It  grows  well  in  agar  cultures  and  especially  in  glycerine  agar,  in 
which  it  produces  some  gas  and  an  acid  reaction.  The  growth  on  the 
surface  of  glycerine  agar  cultures  is  white,  cream-like  in  consistency» 
and  quite  abundant. 

It  grows  well  in  an  agar  or  gelatine  medium,  made  acid  by  the  addi- 
tion of  0.2  per  cent.  (1:500)  of  hydrochloric  acid. 

In  cocoanut  water  it  multiplies  rapidly,  producing  a  milky  opacity  of 
the  previously  transparent  fluid,  an  acid  reaction,  and  an  evolution  of 
carbon  dioxide. 

On  potato  it  produces  a  thick  layer,  which  may  cover  the  entire  sur-^ 
face  in  three  or  four  days,  and  wliich  has  a  dirty- white,  cream-white,  or 
pinkish-white  color,  and  cream-like  consistency.  The  growth  upon  po- 
tato varies  at  different  times,  ovidentl^^  owingto  differences  in  the  potato. 
This  is  shown  by  my  notes  with  reference  to  the  potato  culture  from 
which  my  j)hotomicrograph  was  made.  Fig.  2,  PI.  VI. 

lu  potato  culture,  slide  1681,  negative  573,  bacillus  x  has  gro-^-n  as  a  thin  cream- 
^Yhite  layer;  the  rods  are  longer  than  usual,  and  hare  vacuoles  at  the  ends  as  ob- 
served in  Havana.  Esmarch  roll-tubes  from  this  potato  sho\\'  it  to  be  a  pure  culture 
with  typical  colonies,  one  of  which  (slide  1689)  shows  elements  of  various  lengths, 
some  short  oval.  Another  potato  culture  from  the  above  gives  the  usual  short  oval 
form.  The  growth  of  the  first  potato  with  long  form  is  more  scanty  than  usual,  and 
white  in  color;  the  potato  is  not  discolored;  another  potato  inoculated  from  this  one 
turns  bluish,  the  growth  is  abundant  and  of  a  yellowish-w^hite  color.  The  first  potato 
has  an  acid  reaction,  the  second  is  neutral  or  slightlj^  alkaline. 

The  colonies  in  gelatine  Esmarch  roll-tubes  vary  considerably  at 
different  times.  Deep  colonies  are  usually  spherical,  homogeneous^ 
light-brown  in  color,  and  more  opaque  than  the  similar  colonies  of  the 
colon  bacillus.  At  the  end  of  a  few  days  the  deep  colonies  become 
quite  opaque  and  may  be  lobate  like  a  mulberry,  or  coarsely  granular; 
sometimes  the  deep  colonies  have  an  opaque  central  portion  surrounded 
by  a  transparent  marginal  zone. 

In  old  gelatine  roll-tubes  these  deep  colonies  form  opaque,  white 
hemispheres,  projecting  from  the  surface  of  the  dried  culture  medium^ 
and  little  tufts  of  acicular  crystals  are  sometimes  observed  to  project, 
from  the  side  of  such  old  colonies. 

The  superficial  colonies  are  circular  or  irregular  in  outline,  with  trans- 
parent margins  and  an  opaque  central  portion,  sometimes  corrugated. 
They  are  finely  granular  and  iridescent  by  reflected  light,  and  of  a 


192 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


milk-white  color ;  by  transmitted  light  they  have  a  brownish  color. 
Young  colonies  closely  resemble  those  of  the  colon  bacillus  {a).  This 
bacillus  grows  well  at  a  temperature  of  20°  C.  (GS°  F.),  but  more  rapidly 
$ind  luxuriantly  at  a  higher  temperature,  30°  to  35°  0.  Its  vitality  is 
not  destroyed  bj^  exposure  iu  a  freezing  mixture  of  ice  and  salt  for  2 
hours.  The  thermal  death  point  is  between  140°  and  145°  F.  (60°  to  62° 
0.),  but  to  insure  the  sterilization  of  cultures  contained  in  test-tubes  or 
flasks  I  am  in  the  habit  of  subjecting  them  to  temperature  of  160°  F„ 

Bacillus  X  is  pathogenic  for  rabbits  when  injected  into  the  cavity  of 
the  abdomen. 

This  is  shown  by  the  following  experiments  arranged  in  tabular 
form  : 

INJECTED  INTO  CAVITY  OF  ABDOMEN. 


Eabbit 

ISO. 


108 
109 
111 
120 
121 
125 
126 
127 
132 
157 
166 
190 
192 
193 
208 

210 
221 
222 
223 
224 
234 
235 
244 
255 
259 
260 
293 


Weight 
in  grams. 


small 
large 
1,000 


large 
medium 
...do.... 


1,500 
1,500 
1,100 
1,350 
1,200 
1,425 

1,425 

930 

910 

1,250 

1,330 

945 

1,090 

1,300 

1,250 

1.520 

1,710 

2,270 


Date. 


1889. 
May  22 
May  24 
June  5 
June  27 
June  29 
July  25 
July  25 
July  26 
July  28 
Aug.  8 
Aug.  12 
Nov.  16 
Nov.  18 
Nov.  19 
Dec.   13 

1890. 
Jan.  3 
Jan.  13 
Jan.  13 
Jan.  31 
Jan.  31 
Feb.  26 
Feb.  26 
Mar.  3 
Mar.  10 
Mar.  10 
Mar.  10 
Apr.     2 


Culture. 


Glycerine  agar 
Agar  culture. . 

Veal  broth 

Agua  coco 

....do 

...do 

...do 

....do  

....do  

...do 

....do 

....do 

....do , 

....do 

...do 

...do 

...do 

...do 

Blood  serum. .. 

....do 

...do  

...do 

...do , 

Bouillon 

...do  

...do 

...do 


Amount. 


1  cc. 

1  cc. 
10  cc 
1  cc. 
l^cc 

3  cc 

4  cc. 

3  cc. 

4  cc. 
2-1  cc 
3  cc. 

5  cc. 
3  cc. 
1  cc. 
IJ  cc 

1  cc. 
3  cc. 
3  cc. 
2cc. 

2  cc. 
lice 

ice 
2cc. 
5  cc . 
8cc. 
10  cc 
IJcc 


Result. 


Died  at  end  of  2  hours  and  40  minute 

Result  negative. 

Died  at  end  of  5i  hours. 

Died  at  end  of  31  hours. 

Recovered. 

Died  at  end  of  5  hours. 

Died  at  end  of  2  hours. 

Died  at  end  of  3  hours. 

Died  at  end  of  6  J  hours. 

Died  at  end  of  9J  hours. 

Died  at  end  of  22  hours. 

Died  at  end  of  2i  hours. 

Died  at  end  of  4  hours. 

Died  at  end  of  2  hours. 

Died  at  end  of  3  hours.  • 

Recovered. 

Dead  next  morning. 

Dead  morning  of  Jan.  15  (48  hours). 

Dead  at  end  of  3  hours. 

Dead  next  morning  (22  hours). 

Do 

Do 

Do 
Dead  at  cud  of  3  hour."!. 
Found  dead  next  morning. 

Do 
Died  at  end  of  30  hours. 


SUBCUTANEOUS  INJECTIONS  INTO  RABBITS. 


1889. 

109 

large 

May  20 

Gelatine  culture... 

3  drops  . . . 

Result  negative. 

110 

...do.... 

May   24 

Agar  culture 

2  drops  . . . 

Do. 

112 

June    5 

Veal  broth 

4  cc 

Do. 

119 

June  27 
1890. 

1  cc 

Died  at  end  of  30  hours. 

265 

1,520 

Mar.  13 

2cc 

Result  negative. 

ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 
rNMECTIOXS  INTO  EAR  VEIN"  OF  RABBITS. 


193 


1889. 

210 

],2C0 

Dec.  17 
1890. 

218 

1,180 

Jan.  8 

219 

1,575 

Jan.  8 

Agna  coco. . 

Blood  serum 
Agna  coco.. 


2 minims..    Result  negative. 


3  minima..]        Do. 

4  minims  .         Do. 


The  negative  results  obtained  in  injecting  cultures  beneath  the  skin 
or  into  the  ear  vein  of  rabbits  show  that  this  bacillus  does  not  induce  a 
fatal  septicajinia  in  these  animals,  and  the  fatal  result  when  injections 
are  made  into  the  peritoneal  cavity  does  not  appear  to  be  due  to  an 
invasion  of  the  blood,  but  rather  to  the  local  effects  upon  the  peritoneum 
together  with  the  toxic  action  of  the  chemical  products  resulting  from 
its  growth. 

It  is  true  that  I  have  always  been  able  to  recover  the  bacillus  from 
the  liver,  or  from  blood  obtained  from  one  of  the  cavities  of  the  heart, 
even  in  animals  which  succumb  within  a  few  hours  to  an  injection  made 
into  the  cavity  of  the  abdomen.  But  the  direct  examination  of  the 
blood  shows  that  the  bacilli  are  present  in  very  small  numbers,  and 
leads  me  to  believe  that  the  bacillus  does  not  multiply,  to  any  consid- 
erable extent  at  least,  in  the  circulating  fluid. 

The  spleen  is  not  enlarged,  as  is  the  case  in  anthrax,  rabbit  septi- 
caimia,  and  other  diseases  in  which  the  pathogenic  micro-organism  mul- 
ti]r)lies  abundantly  in  the  blood. 

On  the  other  hand  there  is  evidence  of  local  inflammation  in  the  peri- 
toneal cavity.  When  death  occurs  within  a  few  hours  the  peritoneum 
is  more  or  less  hyper?emic  and  there  is  a  considerable  quantity  of  straw- 
colored  fluid  in  the  cavity  of  the  abdomen.  When  the  animal  lives  for 
24  hours  or  more  there  is  a  decided  peritonitis  with  a  fibrinous  exuda- 
tion u]3on  the  surface  of  the  liver  and  intestine. 

In  the  above  table  it  will  be  seen  that  the  most  of  the  animals  in- 
jected in  the  cavity  of  the  abdomen  died  within  24  hours,  but  I  shall 
shortly  give  some  experiments  in  which  death  occurred  at  a  later  date 
as  a  result  of  a  partial  protection  from  previous  injections  made.  In 
these  cases  the  results  of  a  fibrinous  peritonitis,  with  adhesions,  are 
clearly  seen.  I  have  spoken  of  the  exudation  upon  the  surface  of  the 
liver  and  intestines  in  animals  which  die  at  the  end  of  20  hours  or  more 
as  "  fibrinous."  Under  the  microscope  it  is  seen  to  be  composed  largely 
of  leucocytes,  and  these  commonly  contain  bacilli  in  their  interior,  as  is 
seen  in  my  photo-micrograph.  Fig.  1,  PI.  vi.  Whether  a  genuine  phagy- 
cytosis  occurs  I  have  not  yet  definitely  determined,  but  propose  to  give 
my  attention  to  the  question  hereafter.  In  one  case,  in  which  an  animal 
was  killed  some  days  after  receiving  an  injection  into  the  peritoneal 
cavity,  there  was  evidence  of  fibrinous  peritonitis,  and  the  liver  was 
cirrhotic.  In  several  other  cases  the  liver  has  also  seemed  to  me  to  be 
harder  than  normal,  but  no  defluite  evidence  of  recent  connective  tissue 
40G7 13 


194 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER. 


growth  has  been  made  out  in  thin  sections  of  the  organ.  Usually  the 
liver  in  animals  which  die  within  24  hours  is  full  of  blood,  rather  soft, 
and  dark  in  color.  In  a  single  instance  1  found  the  liver  to  be  of  a  light 
color,  and  loaded  with  fat.  As  the  animal  was  excessively'  fat  and  this 
was  an  exceptional  case,  I  have  not  supposed  that  the  observation  is 
entitled  to  any  special  weight  in  estimating  the  evidence  with  regard  to 
this  bacillus  from  an  etiological  point  of  view. 

The  rapidly  fatal  effect  in  those  cases  in  which  I  have  injected  2  or 
more  cubic  centimeters  of  a  culture  into  the  cavity  of  the  abdomen  has 
led  me  to  suppose  that  death  results  from  the  toxic  effects  of  a  ptomaine 
contained  in  the  culture  at  the' time  of  injection.  The  symptoms  also 
give  support  to  this  supposition.  The  animal  quickly  becomes  feeble 
and  indisposed  to  move,  and  some  time  before  death  lies  helpless  upon 
its  side,  breathing  regularly,  but  is  too  feeble  to  get  up  on  its  feet  when 
disturbed.  Death  sometimes  occurs  in  convulsions,  hut  more  frequently 
without,  apparently  from  heart  failure. 

My  experiments  upon  guinea-pigs  are  given  in  the  following  table. 
They  show  that  this  bacillus  is  less  pathogenic  for  these  animals  than 
for  rabbits. 

Experiments  on  guinea-pigs. 


No. 


66 
78 
104 
119 
121 
155 
162 
163 
168 
169 
170 
171 
172 
189 
190 

204 

205 


Date. 


Culture. 


Amount. 


Where  irjeeted. 


Result. 


1889. 
May  29 
June  3 
Jane  13 
June  24 
June  26 
July  17 
July  21 
July  22 
Nov.  16 
Nor.  18 
.-..do.. 
Nov.  20 
....do  .. 
Dec.  17 
....do  ... 


1890. 
Mar.  10 
...do  ... 


Agua  coco . 
....do 

Glyc.  agar . 

Agua  coco . 

...do 

....do  

...do 

....do  

....do  

....do  

...do 

....do  

...do  

....do  

....do  


Bouillon  . 
..  do... 


Ice. 

^cc. 
Ice. 

2CC. 

^cc. 
J  cc. 
1  cc. 
Jcc. 
2cc. 
3cc. 
4cc. 
ice. 
1  cc. 
Ice. 

6cc. 
2cc. 


Subcut  

....do 

....do 

....do 

....do  

....do  

....do  

....do  

....do 

Cavity  of  abdomen 

....do 

Subcut  

..    do , 

....do  

....do 


Cavity  of  abdomen . 
....do 


Negative. 

Very  sick,  but  recovered. 

Eesult  negative. 

Dead  at  6  a.  m.  next  morning. 

Sick  2  days,  but  recovered. 

Dead  next  morning. 

Result  negative. 

Do. 

Do. 
Dead  at  end  of  20  hours. 

Do. 
Result  negative. 

Do. 

Do. 

Do. 

Dead  at  end  of  18  hours. 
Do. 


I  have  made  the  following  experiments  on  dogs : 

Baltimore,  Noveniber  16,  10:30  a,  m.,  1889. — Injected  into  cavity  of  abdomen  of  small 
puppy,  .3  months  old,  2  cnbic  centimetres  of  a  culture  of  bacillus  x  in  agua  coco.  A.t 
2  p.  m.  the  dog  appeared  quite  sick  and  indisposed  to  move  and  continued  so  during 
the  afternoon.  Temperature  in  rectum  at  4  p.  m.,  104^  F.  November  17,  9  a.  m., 
the  dog  appears  well;  temperature,  100.2- .  November  18th,  continues  well;  tem- 
perature, 101-.     Ou  this  date,  at  10:30  a.  m.,  injected  into  cavity  of  the  abdomen  5 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  195 

cubic  ceutimetres  culture  of  bacillus  x  in  agua  coco.     Temperature  at  3;30  p,  m,. 
102.4'^.     Dog  appears  lively.    Next  day  apparently  well. 

Baltiviore,  November  19,  10:30  a.  m. — lujected  into  cavity  of  abdomen  of  small 
puppy,  5  months  old,  4  cubic  centimetres  culture  of  bacillus  x  in  agua  coco.  Tem- 
perature just  before  injection,  102.4°;  temperature  at  3  p.m.,  103.8°;  the  animal  is 
evidently  sick  and  lies  quietly  in  its  box.  November  20,  10  a.  m.,  seems  better,  but 
stiU  quiet;  temperature,  102.6°.  November  21,  jumps  about  and  appears  perfectly 
well. 

EXPERIMENTS  WITH   CULTURES   STERILIZED   BY  HEAT. 

Havana,  July  26,  1889. — lujected  into  cavity  of  abdomen  of  rabbit  129,  4  cubic 
centimetres  sterile  culture  bacillus  x  in  agua  coco.     Result  negative. 

Jidy  28,  1889. — Injected  into  cavity  of  abdomen  of  rabbit  No.  130,  8  cubic  centi- 
metres sterile  culture  of  bacillus  x  in  agua  coco.     Result  negative. 

July  30,  1889. — Injected  into  cavity  of  abdomen  of  rabbit  137  8  cubic  centimetres 
sterile  culture  bacillus  x  in  agua  coco.     Result  negative. 

July  30,  1889. — Injected  into  cavity  of  abdomen  of  rabbit  138  10  cubic  centimetres 
sterile  culture  bacillus  x  in  agua  coco.     Result  negative. 

August  21,  1889. — Injected  into  cavity  of  abdomen  of  rabbit  182,  weight  1,000  grams, 
7  cubic  centimetres  sterile  culture  bacillns  x  in  agua  coco.    Result  negative. 

These  experiments  show  that  the  death  of  auimals  which  have  re- 
ceived iu  the  cavity  of  the  abdomen  2  or  3  cubic  centimetres  of  a  uon- 
sterilized  culture  of  bacillus  x  is  not  due  alone  to  the  toxic  action  of  a 
ptomaine  present  in  the  culture,  but  depends  upon  the  presence  of  the 
living  bacilli,  unless  in  the  process  of  sterilization  at  160°  F.  the  ptoma- 
ine has  been  destroyed.  The  latter  supposition  is  worthy  of  attention, 
and  the  question  may  be  determined  experimentally  bj'^  injecting  cul- 
tures from  which  the  bacilli  have  been  removed  by  filtration. 

I  have  made  a  few  experiments  with  a  view  to  determining  whether 
animals  which  have  received  full  doses  of  sterilized  cultures  have  any 
subsequent  immunity  from  the  effects  of  non-sterilized  cultures. 

Baltimore,  Nov.  28,  1889. — Injected  into  cavity  of  abdomen  of  rabbit  198  6  cubic 
centimetres  sterile  culture  bacillus  x  (animal  weighs  1,000  grams).  December  11,  9 
a.  m.,  injected  into  cavity  of  abdomen  2  cubic  centimetres  culture  bacillns  x  in  agua 
coco.     The  animal  died  at  the  end  of  7  hours  after  receiving  this  injection. 

Baltimore,  March  4, 1890. — Injected  into  cavity  of  abdomen  of  rabbit  No.  274,  weight 
1,480  grams,  5  cubic  centimetres  sterile  culture  bacillus  x  in  bouillon  with  5  per  cent 
glycerine.  March  10,  9  a.  m,  animal  in  good  health,  weighs  1,375  grams.  Injected 
into  cavity  of  abdomen  4  cubic  centimetres  culture  bacillus  x  in  bouillon  with  5  per 
cent,  of  glycerine.    Dead  next  morning  at  8  o'clock. 

March  6,  1890. — Injected  into  cavity  of  abdomen  of  rabbit  2.51,  weight  2,170  grams, 
10  cubic  centimetres  sterile  culture  bacillus  x  in  bouillon  with  5  per  cent,  glycerine. 
March  10,  9  a.  m.,  the  animal  appears  well ;  weight  1,750  grams.  Injected  in  cavity 
of  abdomen  5  cubic  centimetres  culture  bacillus  x  with  5  per  cent,  glycerine.  Died 
in  convulsions  at  8.30,  March  12. 

March  13,  1890. — Injected  into  cavity  of  the  abdomen  of  rabbit  266,  weight  640 
grams,  4  cubic  centimetres  sterile  culture  bacillus  x  in  bouillon  with  5  per  cent, 
glycerine.  March  18,  9.30  a.  m.,  in  good  health;  weight  610  grams.  Injected  into 
cavity  of  abdomen  2  cubic  centimetres  bouillon  culture  bacillns  x.  March  22,  10  a. 
m  ,  iu  good  health;  weight  610  grams.  Killed  and  abdominal  viscera  found  to  be  nor- 
mal in  appearance. 

March  13,  1890,  12  in. — Injected  into  cavity  of  abdomen  of  rabbit  267,  weight  645 


196     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

grams,  4  cubic  centimetres  sterile  culture  bacillus  x  in  bouillon  with  5  percent, 
glycerine.  March  18,  remains  Tvell ;  weight  GIO  grams.  Injected  into  cavity  of  abdo- 
men 2  cubic  centimetres  bouillon  culture  bacillus  x  -with  5  per  ceut.  glycerine. 
Animal  died  at  .3  p.  m.  nest  day. 

March  10, 1S90. — Injected  into  cavity  of  abdomen  of  rabbit  Xo.  282,  weight  1,100 
grams,  12  cubic  centimetres  sterile  culture  bacillus  x,  in  bouillon  with  5  per  ceut. 
glycerine.  March  22,  11  a.  m.,  remains  in  good  health;  weight  1,030  grams.  Injected 
in  cavity  of  abdomen  5  cubic  centimetres  culture  bacillus  x  in  bouillon  with  5  per 
cent,  glycerine.     Found  dead  next  morning;   intense  fibrinous  peritonitis. 

It  will  be  seen  that  these  experiments  give  somewhat  contradictory- 
results  ;  some  of  the  animals  survived  a  lethal  dose  of  a  nonsterilized 
culture  after  having  received  a  full  dose  of  a  sterile  culture,  and  others 
did  not.  But  in  those  which  succumbed  the  time  of  death  appears  to 
have  been  delayed.  Thus  in  experiment  of  March  13  a  small  rabbit 
which  received  at  noon  2  cubic  centimetres  of  a  nonsterilized  culture 
did  not  die  until  3  o'clock  the  next  day,  while  another  rabbit  of  about 
the  same  size  survived  the  injection  of  a  similar  amount  (March  13). 
In  another  experiment  (March  6)  a  large  rabbit  received  a  dose  (5  cubic 
centimetres)  which  usually  kills  within  3  or  4  hours,  but  died  at  the 
end  of  48  hours. 

Still  the  experiments  as  a  whole  do  not  give  satisfactory  e^idence  of 
immunity  as  a  result  of  the  injection  of  sterilized  cultures,  and  T  am 
inclined  to  look  upon  the  partial  immunity  afforded  as  due  rather  to  a 
tolerance  on  tlie  ixirt  of  the  j^erifoneum  than  to  a  general  tolerance  of  the 
toxic  ijroducts  present  in  cultures  of  this  bacillus.  This  view  is  sup- 
ported by  the  fact  that  I  have  had  even  more  decided  evidence  of  im- 
munity from  the  previous  injection  into  the  cavity  of  the  abdomen  of 
other  bacilli. 

This  is  shown  by  the  following  experiments  : 

March  10,  1890.— Injected  subcntaneously  into  rahbit  258  1  cubic  centimetre  lif^ue- 
fied  gelatin  culture  of  bacillus  pyocyanus.  March  22,  10  a.  m.  weight  2,085  grammes ; 
injected  into  cavity  of  abdomen  2  cubic  centimetres  liquefied  gelatiu  culture  of  bacil- 
lus pyocyanus.  March  27,  2p.  m.,  in  good  health,  weight  1,675  grammes :  injected  into 
cavity  of  abdomen  4  cubic  centimetres  culture  of  bacillus  x  in  boriillon  with  5  per 
cent,  glycerin.  April  2,  11  a.  m.,  weight  1,735  grammes;  injected  into  cavity  of 
abdomen  4  cubic  centimetres  culture  bacillus  x  in  bouillon  with  5  per  cent,  of  glycerin. 
No  result. 

March  10. — Injected  into  cavity  of  abdomen  of  rabbit  No.  255,  weight  2,120  grammes, 
10  cubic  centimetres  sterile  culture  of  bacillus  acidiformans.  March  18,  10  a.  m., 
weight  1,300  grammes;  injected  into  cavity  of  abdomen  5  cubic  centimetres  culture 
Lacillus  X  in  bouillon  with  5  per  cent,  of  glycerin.  March  22,  weight  1,290  grammes; 
thin  and  rather  weak  :  killed ;  some  evidence  of  peritonitis;  liver  ajipareutly  cirrhotic. 

March  15. — Injected  into  cavity  of  abdomen  of  rabbit  No.  275,  weight  550  grammes, 
one-half  cubic  centimetre  liquefied  gelatin  culture  of  bacillus  36.  March  22,  weight 
630  grammes;  injected  into  cavity  of  abdomen  1  cubic  centimetre  culture  bacillus  x  in 
bouillon  with  5  per  cent,  glycerin.  March  27,  remains  well;  weight  750  grammes; 
injected  into  cavity  of  abdomen  2  cubic  centimetres  bouillon  culture  of  bacillus  x. 
Found  dead  on  the  morning  of  March  29. 

Note, — As  a  rule,  2  cubic  centimetres  of  the  culture  of  bacillus  x  would  kill  a 
rabbit  of  this  size  within  4  hours.  We  liave,  therefore,  evidence  of  a  certain  degree 
of  tolerance  as  a  result  of  the  jirevious  injections. 


ETIOLOGY    AND    PRP:YEXTI0X    OF    YELLOW    FEVER.  197 

March  17,  1890.— Injected  subcntaueously  into  rabbit  Xo.  270,  weight  .ol5  grammes, 
1  cubic  centimetre  bouillon  culture  of  bacillus  gracilis.  March  2'2,  in  good  health  ;  in- 
jected into  cavity  of  abdomen  2  cubic  centimetres  culture  bacillus  gracilis  in  bouil- 
lon. March  27,  weight  560  grammes  ;  injected  into  cavity  of  abdomen  2^  cubic  centi- 
metres culture  bacillus  x  in  bouillon  with  5  per  cent,  glycerin.  Animal  remains  in 
good  health  April  20. 

March  18.— Injected  subcutaneously  into  rabbit  277,  weight  1,740  grammes,  li  cubic 
centimetres  bouillon  culture  Clostridium  cadaverinus.  March  22,  weight2,010  grammes; 
injected  into  cavity  of  abdomen  2  cubic  centimetres  bouillon  culture  bacillus  gracilis. 
March  27,  weight  1,690  grammes ;  injected  into  cavity  of  abdomen  3  cubic  centimetres 
culture  bacillus  x  in  bouillon  with  5  per  cant,  of  gelatine.  April  2,  weight  1,700 
grammes;  injected  in  cavity  of  abdomen  4  cubic  centimetres  culture  bacillus  x  in 
bouillon  with  .5  per  cent,  glycerin.  April  4,  in  good  health  :  killed  at  11  a.  m. :  some 
fibrinous  exudation  upon  surface  of  liver,  intestine,  and  spleen;  cirrhosis  of  liver. 

March  18, 1890. — Injected  subcutaneously  into  rabbit  So.  279,  weight  690  grammes,  3 
cubic  centimetres  bouillon  culture  of  bacillus  xjyocyanus.  March  22,  11  a.  m.,  weight 
780  grammes  ;  injected  into  cavity  of  abdomen  2  cubic  centimetres  liquefied  gelatin 
culture  bacillus  pyocyanus.  March  27,  1  p.  m,,  weight  795  grammes ;  injected  into 
cavity  of  abdomen  3  cubic  centimetres  culture  of  bacillus  x  in  bouiUon  with  5  per 
cent,  glycerin.     Animal  died  at  1  p.  m.,  March  28. 

March  18,  1890. — Injected  into  cavity  of  abdomen  of  rabbit  Xo.  280,  weight  940 
grammes,  5  cubic  centimetres  .sterile  culture  of  bacillus  gracilis  in  bouillon.  March 
22,  weight  1,060  grammes;  injected  into  cavity  of  abdomen  3  cubic  centimetres  bouil- 
lon culture  of  bacillus  gracilis  (not  sterilized).  March  27,  weight  1,155  grammes; 
injected  into  cavity  of  abdomen  2  cubic  centimetres  culture  of  bacillus  x  in  bouillon 
with  5  per  cent,  of  glycerin.  April  2,  weight  l,0d0  grammes;  injected  into  cavity  of 
abdomen  4  cubic  centimetres  culture  bacillus  x  in  bouillon  with  5  per  cent,  glycerin. 
April  4,  in  apparent  good  health  :  killed  at  10  a.  m. :  no  peritonitis,  no  development  in 
gelatin  stick  culture  from  liver. 

Note. — Alarger  rabbit,  weight  2,270  grammes,  succumbed  to  an  injection  of  1^  cubic 
centimetres  of  the  same  culture,  injected  on  the  2d  of  April,  at  the  end  of  29  hours. 
In  this  animal  the  autopsy  revealed  an  intense  fibrinous  peritonitis. 

March  31,  1890. — Injected  into  cavity  of  the  abdomen  of  rabbit  Xo.  283,  weight 
1,220  grams,  1  cubic  centimetre  culture  bacillus  gracilis  in  bouillon.  April  4,  11  a. 
m.,  weight  1,140  grammes ;  injected  into  cavity  of  abdomen  4  cubic  centimetres  culture 
bacillus  X  in  bouillon  with  5  peT  cent,  of  glycerin.  Found  dead  at  8  o'clock  next 
morning;  some  peritonitis  and  considerable  fluid  in  cavity  of  abdomen. 

March  31,  1890. — Injected  into  cavity  of  abdomen  of  rabbit  234,  weight  1,560 
grammes,  1  cubic  centermetre  bouillon  culture  of  bacillus  gracilis.  April  4,  11  a.  m. 
weight  1,425  grammes;  injected  into  cavity  of  abdomen  4  cubic  centimetres  culture 
bacillus  X  in  bouillon  with  5  per  cent  of  glycerin.     Animal  survived  injection. 

March  31. — Injected  into  cavity  of  abdomen  of  rabbit  285,  weight  910  grammes,  1|- 
cubic  centimetres  bouillon  culture  bacillus  gracilis.  April  4,  11  a.  m.,  weight  980 
grammes ;  injected  into  cavity  of  abdomen  4  cubic  centimetres  culture  of  bacillus  x  in 
bouillon  with  5  per  cent,  of  glycerin.  Animal  died  on  fourth  day  after  injection. 
April  8,  at  2  p.  m.,  no  peritonitis. 

March  31,  1890. — Injected  subcutaneously  into  rabbit  286,  weight  1,280  grammes,  2 
cubic  centimetres  culture  of  bacillus  gracilis  in  bouillon.  April  4.  11  a.  m.,  weight 
1,240  grammes  ;  injected  into  cavity  of  abdomen  4  cubic  centimetres  culture  bacillus  x 
in  bouillon  with  5  per  cent,  of  glycerin.  Animal  found  dead  on  the  morning  of 
April  11  :  no  xjeritonitis.  Bacillus  of  rabbit  septicaemia  obtained  in  culture  from 
liver. 

Note. — It  is  ydobable  that  the  preceding  rabbit  also  died  from  rabbit  septictr-mia 
which  at  this  date  carried  off  a  number  of  rabbits  kept  in  the  same  cage,  among 
others,  three  which  had  injected  in  the  cavity  of  the  abdomen  a  sterilized  culture  of 


198  ETIOLOGY    AND    PEEVENTION    OF    YELLOW    FEVER. 

■bacillus  pyocvanns.  Pure  cnltures  of  bacillus  caniciilacida -^vere  obtaiued  from  the 
blood  of  all  of  these. 

I  have  made  a  few  exijeriments  to  determine  Tvbetlier  any  protection 

is  aiibrded  by  sul3cutaueous  injections  or  injections  in  the  ear  vein* 
These  are  given  below. 

Deceni?»erl7, 1889.— Injected  into  the  ear  vein  of  rabbit  No.  210, -weight  1,260  gramraesj 
2  drops  of  culture  bacillus  x  in  agua  coco.  January  3,  10  a.  m.,  injected  into  cavity 
of  abdomen  1^^  cubic  centimetres  culture  of  bacillus  x  in  agua  coco  :  February  3,  10  a^ 
m.,  weight  8-50  grammes,  verj-  thin  and  feeble:  iujected.  into  cavity  of  abdomen  2 
cubic  centimetres  culture  of  bacillus  x  in  blood  serum.     Dead  next  morning. 

December  17,  1889. — Injected  iuto  the  ear  vein  of  rabbit  211  4  drops  of  culture  of 
bacillus  X  in  agua  coco.  January  3,  10  a.  m.,  injected  into  cavity  of  abdomen  1  cubic 
centimetre  culture  bacillus  x  in  agua  coco.  Found  dead  on  the  morning  of  January 
8  (5  days).     No  peritonitis,  no  bacilli  found  in  liver. 

January  8,  1S90. — Iujected  into  ear  vein  of  rabbit  218,  weight  1,180  grammes,  3  drops 
of  cultuie  of  bacillus  x  in  blood  serum.  Februry  3,  10  a.  m,,  weight  1,710  grammes, 
injected,  into  cavity  of  abdomen  2  cubic  centimeters  culture  of  bacillus  x  in  blood 
serum  kejit  in  oven  at  20-  C.for  20  days.  February 6,  10  a.  m.,  weight  1,600 grammes; 
injected  into  cavity  of  abdomen  5  cubic  centimetres  culture  bacillus  x  in  bouillon 
with  5  per  cent,  glycerine  in  oven  at  3.5°  C.  for  3  days.  Dead  next  morning  at  8 
o'clock. 

March  13,  1890. — Injected  iuto  ear,  not  in  vein  but  into  connective  tissue,  5  drops 
of  a  bouillon  culture  of  bacillus  x.  March  18,  10  a.  m.,  weight  2,010  grams  :  injected, 
into  cavity  of  abdomen  3  cubic  centimetres  bouillon  culture  bacillus  x.  Dead  nest 
morning  at  8  o'clock. 

Alarch  13, 1890. — Injected,  subcntaneously  into  left  side  of  rabbit  26.5,  weight  1,.520 
grammes,  2  cubic  centimetres  bouillon  culture  of  bacillus  x.  March  18.  in  good  health, 
weight  1,450  grammes  injected  into  cavity  of  abdomen  4  cubic  centimetres  culture 
bacillus  X  in  bouillon  with  5  per  cent,  of  glycerine.  March  22, 10  a.  m.,  in  good  health, 
weight  1,320  grammes.     Killed,  some  fibrinous  peritonitis. 

In  the  following  experiment  a  rabbit  which  survived  the  injection  of 
1  cubic  centimetre  in  the  cavity  of  the  abdomen  succumbed  at  a  later 
date  to  a  larger  quantity  : 

.Jan!(a?-y  3, 1890. — Injected  into  the  canity  of  the  abdomen  of  rabbit  216,  weight 
1,425  grammes,  1  cubic  centimetre  of  a  culture  of  bacillus  x  in  agua  coco.  February 
3, 10  a.  m.,  the  animal  has  had  an  abscess  in  the  middle  of  belly  and  is  now  very  thin, 
weight  980  grammes:  injected  into  cavity  of  abdomen  2  cubic  centimetres  culture  bacil- 
lus X  in  blood  serum.  Died  at  12  m.,  February  4.  Adhesions  of  intestine  from  old 
peritonitis ;  considerable  fluid  in  cavity  of  abdomen  ;  liver  very  small  and  rather  dark 
in  color. 

Experiment  of  March  13  gives  evidence  of  immunity  resulting  from  a 
subcutaneous  injection,  but  more  exj^eriments  are  necessary  to  estab- 
lish this  point. 

The  experiments  in  this  series  do  not  support  the  idea  that  an  infec- 
tious disease  is  produced  in  the  rabbit  by  inoculating  it  with  cultures 
of  bacillis  x,  but  a  partial  immunity  from  the  effects  of  intra-peritoneal 
injections  api)ears  to  result  from  previously  introducing  the  bacillus 
into  the  circulation. 

As  already  stated  the  evidence  favors  the  view  that  death  results 
from  peritonitis  fand  toxfemia  ?)  induced  by  intraperitoneal  injections, 
and  that  a  tolerance  on  the  part  of  the  peritoneum  may  be  established  by 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  199 

the  injection  of  cultures  of  certain  other  bacilli,  or  of  sterilized  cultures  of 
bacillus  X. 

I  have  also  made  a  nnmber  of  experiments  with  a  view  to  determine 
the  effects  of  temperature  upon  the  virulence  of  cultures  of  this 
bacillus. 

FEEEZINa  DOES  NOT  DESTBOY  VIRULENCE. 

February  5,  1890,  10  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  No.  228, 
weight  775  grammes,  2  cubic  centimetres  culture  of  bacillus  x  in  blood  serum,  frozen 
for  2  hours  in  ice  and  salt  inixture.  Dead  next  morning  at  8  o'clock.  Bacillus  x  in 
pure  culture  recovered  from  liver. 

February  5,  1890,  10  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  229,  weight 
810  grammes,  2  cubic  centimetres  culture  bacillus  x  in  blood  serum,  frozen  2  hours  in 
ice  and  salt  mixture.  Dead  next  morning  at  8  o'clock.  Bacillus  x  in  pure  culture 
recovered  from  liver. 

For  the  following  experiments  the  cultures  were  made  at  a  tempera- 
ture  of  20°  C. 

January  31,  1890,  9:30  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  223, 
weight  1,250  grammes,  2  cubic  centimetres  culture  bacillus  x  in  blood  serum,  No.  5  of  a 
series  cultivated  at  intervals  of  3  days  in  incubating  oven  at  20*^  C.  Found 
dead  on  return  to  laboratory  at  12:30  a,  m. 

February  26,  1890,  9:30  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  234, 
weight  945  grammes,  li  cubic  centimetres  culture  bacillus  x  in  blood  serum,  No.  8  of  a 
series  at  20'^  C. ;  culture  was  22  days  old  at  time  of  injection.  Animal  dead  next 
morning  at  8  o'clock. 

February  2(3,  1890,  9:30  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  335, 
weight  1,090  grammes,  one-half  cubic  centimetre  culture  bacillus  a;  in  blood  serum 
(same  culture  as  used  for  rabbit  234),  culture  No.  8  of  series  at  20^  C,  22  days  old. 
Animal  dead  next  morning  at  8  o'clock. 

For  the  following  experiments  the  cultures  were  made  at  a  tempera* 
ture  of  35°  C: 

January  3,  1890,  9:30  a.  in. — Injected  into  cavity  of  abdomen  of  rabbit  No.  229, 
weight  1,330  grammes,  2  cubic  centimetres  culture  bacillus  x  in  blood  serum,  No.  5  of 
series  at  35^  C,  culture  3  days  old.  Animal  found  dead  next  morning  at  8  o'clock. 
Pure  culture  of  bacillus  x  from  fluid  in  peritoneal  cavity. 

February  3,  1890. — ^.Injected  into  cavity  of  abdomen  of  rabbit  No.  227,  weight  955 
grammes,  2  cubic  centimetres  culture  of  bacillus  x  in  blood  serum,  No.  3  of  series  at 
35°  C,  culture  12  days  old.  Animal  survived  injection,  and  on  March  5  weighed 
1,340  grammes.  At  10  a.  m.  this  date  injected  into  cavity  of  abdomen  4  cubic  cen- 
timetres culture  bacillus  x  in  bouillon  with  5  per  cent,  glycerine,  3  days  in  oven  at 
35°  C.     Animal  dead  next  morning  at  8  o'clock. 

February  27,  1890. — Injected  into  cavity  of  abdomen  of  rabbit  232,  weight  920 
grammes,  H  cubic  centimetres  culture  bacillus  x  in  blood  serum,  No.  8  of  series  at 
35°  C,  culture  22  days  old.  Animal  survived  injection,  and  on  March  6  weighed  850 
grammes.  10  a.  m.  injected  into  cavity  of  abdomen  4  cubic  centimeters  culture 
bacillus  X  in  bouillon  with  5  per  cent,  of  glycerine.  Found  dead  next  morning  at 
8  o'clock. 

February  27,  1890,  9:30  a.  m. — Injected  into  cavity  of  the  abdomen  of  rabbit  No.  233, 
weight  895  grammes,  1  cubic  centimetre  culture  bacillus  x  in  blood  serum,  No.  8  of 
series  at  35°  C.  (same  as  used  for  rabbit  232),  culture  22  days  old.  Animal  died  at 
7:30  p.  m. 


200     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

The  experimcDts  in  this  series  indicate  that  virulence  is  diminished 
bj' keeping  a  culture  for  some  time  at  35°  C,  but  show  that  the  animals 
which  survived  an  intra-peritoneal  injection  with  these  attenuated  cul- 
tures are  not  protected  from  the  lethal  effects  of  a  recent  culture. 

I  would  say  finally  with  reference  to  this  bacillus  that  I  have  not 
encountered  it  in  my  comparative  researches  made  by  the  same  methods 
upon  cadavers  from  other  diseases  than  yellow  fever. 

In  a  single  instance  I  obtained  bacillus  a?  in  a  culture  from  the  liver 
of  guinea  pig  179,  inoculated  with  3  drops  of  material  from  the  liver  of 
a  case  of  tuberculosis  kept  48  hours  in  an  antiseptic  wrapping. 

The  animal  died  on  the  sixth  day  after  receiving  the  inoculation  and 
I  recovered  from  the  effused  serum  in  the  subcutaneous  connective 
tissue,  a  bacillus  which  presented  all  the  characters  of  bacillus  x.  A 
culture  of  this  bacillus  in  agua  coco  killed  rabbit  205  in  7  hours  (3 
cubic  centimetres)  and  rabbit  207  in  4  hours  (2J  cubic  centimetres). 
This  seemed  to  exclude  bacillus  x  from  further  consideration  as  the 
possible  etiological  agent  in  yellow  fever  5  but  upon  referring  to  the 
history  of  this  guinea  pig  I  found  that  it  had  been  inoculated  a  week 
previously  with  a  culture  of  bacillus  x  (one-half  cubic  centimetres 
injected  subcutaneously,  iS"ovember  20,  at  10  a.  m.). 

It  will  be  remembered  that  the  guinea  pig  is  not  killed  by  sub- 
cutaneous injections  of  cultures  of  this  bacillus.  To  test  the  question 
as  to  whether  bacillus  x  could  survive  for  some  days  in  the  tissues 
of  an  inoculated  guinea  pig,  I  made  the  following  experiments: 

Decemier  17,  18S9,  9  a.  m. — Injected  subcutaneously  into  guinea  pig  No.  189  1  cubic 
centimetre  culture  bacillus  x  in  agua  coco.  The  animal  remained  in  apparent  good 
health,  and  was  killed  at  11  a.  m.  December  23.  Cultures  were  made  from  its  liver  and 
spleen;  in  both  bacillus  x  was  obtained  in  pure  culture. 

The  experiment  was  made  in  duplicate,  1  cubic  centimetre  of  the  same 
culture  having  been  injected  into  guinea  pig  190.  The  animal  was 
killed  at  the  same  time,  and  cultures  made  from  the  liver  and  spleen 
contained  bacillus  x. 

No  3.  Bacillus  acidiformans. — (My  bacillus  i  of  1888.) 

This  bacillus  I  first  obtained  in  June,  1888,  from  a  i^iece  of  yellow- 
fever  liver  which  had  been  preserved  for  48  hours  in  an  antiseptic  wrap- 
ping; it  was  associated  with  bacterium  coli  commune  and  my  bacillus 
cadaverinus.  I  have  since  obtained  it  from  liver  preserved  in  the  same 
way  in  two  of  my  comparative  autopsies. 

It  is,  therefore,  excluded  as  far  as  the  etiology  of  yellow  fever  is  con- 
cerned, but  as  it  is  j)athogenic  and  has  some  interesting  characters  I 
have  given  some  time  to  its  study. 

The  morphology  of  this  bacillus  is  shown  by  my  XDhotomicrograpb, 
Fig.  1,  PI.  VII.  It  is  larger  than  my  bacillus  x,  and  like  it  differs  con- 
siderably in  its  dimensions  at  different  times  ;  the  diameter  may  be  as 
much  as  IJ  /x.  Usually  it  has  the  appearance  of  a  short  rod,  one  and  a 
half  to  two  times  as  long  as  broad,  but  the  elements  are  often  oval  in 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  201 

form.  It  is  oiot  motile.  Like  tbe  colon  bacillus  and  bacillus  x  it  is  a 
facultative  anaeroMc,  and  like  tbera  it  grows  freelj- in  an  acid  medium — 
flesli -peptone-gelatine  containing  0.2  j^er  cent,  of  bydrocbloric  acid.  In 
cultures  containing  glycerine  or  sugar  it  produces  an  abundant  evolu- 
tion of  carbon  dioxide  and  a  volatile  acid  is  formed.  Bouillon  cultures 
to  wliich  5  per  cent,  of  glycerine  has  been  added,  and  which  have  been 
carefully  neutralized,  acquire  a  decidedly  acid  reaction  as  a  result  of 
the  growth  in  them  of  this  bacillus,  but  without  the  addition  of  glycer- 
ine no  acid  is  formed.  I  therefore  infer  that  it  has  the  power  of  break- 
ing up  glycerine,  and  have  named  it  hacillus  acidiformans.  In  cocoanut 
water,  which  contains  glucose,  it  produces  an  intensely  acid  reaction 
and  an  abundant  evolution  of  carbon  dioxide. 

It  does  not  liquefy  gelatine,  and  in  stick  cultures  grows  abundantly 
both  on  the  surface  and  along  the  line  of  puncture.  At  the  end  of  24 
hours  at  22°  C.  a  rounded  white  mass  is  formed  upon  the  surface  re- 
sembling the  growth  of  Friedlander's  bacillus ;  at  the  bottom  of  the 
line  of  j)uncture  the  separate  colonies  are  spherical,  opaque,  and  pearl- 
like by  reflected  light.  Gas  bubbles  are  formed  in  the  gelatine.  (See 
Fig.  8,  PI.  VII.)  At  the  end  of  a  week  the  surface  is  covered  with  a 
thick  white  semi-fluid  mass. 

In  gelatine  roll  tubes  the  superficial  colonies  are  translucent  or  opaque 
and  spherical  or  somewhat  irregular  in  outline  ;  by  reflected  light  they 
are  slightly  irridescent ;  the  deep  colonies  are  spherical,  opaque,  and; 
homogeneous. 

The  growth  upon  the  surface  of  nutrient  agar  is  abundant  and  rapid,, 
of  a  shining  milk-white  color,  and  cream-like  in  consistency.  An  abun- 
dant development  forms  along  the  line  of  puncture  and  the  culture 
medium  is  split  up  by  gas  bubbles.  In  glycerine  agar  the  evolution  of 
gas  is  very  abundant  and  the  culture  medium  acquires  an  intensely 
acid  reaction. 

On  potato  the  growth  is  abundant  and  rapid  at  a  temperature  of  20°- 
to  30°  C,  forming  a  thick,  semi-fluid  mass  of  a  milk-white  color. 

I  have  not  obtained  any  evidence  that  this  bacillus  forms  spores;: 
the  cultures  are  sterilized  by  10  minutes'  exposure  to  a  temperature  of 
160°  F. 

When  cultivated  in  bouillon  to  which  5  per  cent,  of  glycerine  has  been; 
added  the  culture  medium  acquires  a  milky  opacity  and  there  is  a  copi- 
ous precipitate,  of  a  viscid  consistency,  consisting,  of  bacilli :  during  the 
period  of  active  development  the  surface  is  covered  with  gas  bubbles, 
as  in  a  saccharine  liquid  undergoing  alcoholic  fermentation,  and  the: 
liquid  has  a  decidedly  acid  reaction. 


202 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


Pathogenic  for  rabbits  and  guinea  ings. — This  is  sbowu  by  the  follow- 
iug  experimeuts: 


Animal.- 

Date. 

Culture. 

Amount 

"Where  injected. 

Result. 

Guinea  pig  . . 
Do 

1888. 
Aug.  31 
Aug.  31 
Sept    3 
Sept    1 
Sept.    4 
Sept.    6 
Sept    7 
Sept    7 
Sept    7 
Sept.  11 

1889. 
TSov.  12 
Dec.  24 
Dec.   24 

1890. 
Feb.   15 
Feb.  28 
Mar.     1 
Miir.     1 
Mar.     3 
Mar.     3 

Potato 

....do 

Small  ... 
...do  .... 

Cavity  of  abdomen  . .. 

....do  

do 

Died  at  end  of  27  hours. 

Rabbit 

Bouillon 

..-.do 

...do 

....do  

....do 

....do  

....do  

....do  

Agua  coco... 

...do 

....do  

....do 

Bouillon 

Blood  serum 
....do 

Bouillon 

Blood  serum. 

2  cc 

Died  on  fourth  day. 

Guinea  pig  .. 
Do 

2  cc 

...do    . 

3  cc 

do 

Babbit 

IJ  cc 

1  cc 

J  cc 

....do 

Do 

Do 

Subcutaneous 

....do  

Died  on  seventh  day. 
Do. 

Do 

Guinea  pig  . . 

\  cc 

2  cc 

Cavity  of  abdomen  . . . 
....do .-. 

Died  on  fifth  day. 
Died  at  end  of  28  hours. 

Eabbit 

....do 

Do 

Do 

1\  cc... 

....do 

....do  

Do. 
Died  at  end  of  28  hours. 

Do 

....do 

Do 

2  cc 

do 

Died  at  end  of  9  hours. 

Do 

]J  cc... 

....do 

Died  at  end  of  22  hours. 

Do 

....do  

Do. 

Do 

2  CO  . .. 

do 

Died  at  end  of  20  hours. 

Do 

2  cc 

do 

Do. 

The  following  exjjeriuieuts  have  been  made  with  sterilized  cultures  of 
this  bacillus: 


Animal. 

Date. 

Culture. 

Amount. 

"Where  injected. 

Result. 

Eabbit 

1890. 
Mar.    4 
Mar.  10 
Mar.  10 
Apr.    1 
Apr.    1 

Bullion 

....do 

5  cc. 
10  cc. 
10  cc. 
10  cc. 
10  cc. 

Negative. 
Do. 

Do 

Do 

....do  

....do  

do 

Do. 

Do 

...do 

....do 

Do. 

Do 

do 

Do. 

In  animals  which  succumb  to  an  intra-peritoneal  injection  of  a  cul- 
ture of  this  bacillus  the  intestine  is  commonly  hypertemic,  the  spleeu 
enlarged,  the  liver  normal.  The  bacillus  is  found  in  the  blood  in 
rather  small  numbers,  and  may  always  be  obtained  in  cultures  from 
the  blood  or  the  parenchyma  of  the  liver  or  spleen. 

No.  4.  Bacillus  cavicida  Havanieusis.     (My  bacillus  x  x  Havana,  l5i89.) 

This  bacillus  was  obtained  from  the  contents  of  the  intestine  of  a 
yellow  fever  cadaver  in  Havana,  in  1889  (Autopsy  No.  24),  through  in- 
oculated guinea-pigs,  as  follows : 

June  13,  12  m. — lujected  snbcutaneously  into  gninea-pig  No.  102,  3  minims  of  viscid 
mucus  from  intestine  of  Case  24  ;  collected  at  9  a.  m.  ;  not  black.  The  animal  died 
at  8.30  a.  m.,  June  14  ;  considerable  collection  of  bloody  serum  in  subcutaneous  con- 
nective tissue  containing  a  motile  bacillus.   June  14, 10  a.  m.,  injected  snbcutaneously, 


ETIOLOGY    AND    PREVENTION    OP    YELLOW    FEVEE.  203 

into  guinea-pig  105,  3  minims  of  bloody  serum  from  cellular  tissue  of  guinea-pig  102. 
Jujie  15,  6  a.  m.,  the  animal  is  very  feeble,  lying  upou  its  side,  respiration  rapid. 
Died  at  7.30  a.  ra.;  autopsy  at  once.  No  subcutaneous  cedema,  liver  pale,  abdominal 
viscera  normal  in  appearance ;  bacilli  in  smear-preparation  from  liver;  a  few  in  prep- 
aration from  blood  of  heart.  Pure  culture  of  motile  bacillus  from  blood  of  heart; 
slide  1241. 

This  is  an  actively  motile,  non-liquefying  hacillus. 

It  is  a  facultative  anaerobic.  In  gelatine  stick-cultures  the  growth 
upon  the  surface  is  very  scanty  and  thin,  not  extendiug  far  from  the 
point  of  puncture  5  along  the  line  of  puncture  are  developed  small 
translucent,  pearl-like,  spherical  colonies,  which  later  become  opaque 
and  sometimes  granular. 

In  gelatine  roll-tubes,  at  the  end  of  24  hours  at  22°  C,  the  deep  colo- 
nies are  very  small  spheres  Of  a  pale  straw-color,  later  they  become 
opaque  light-brown  spheres,  or  may  have  a  dark  central  mass  sur- 
rounded by  a  transparent  zone.  The  superficial  colonies  at  the  end  of 
5  days  are  small  translucent  masses  of  a  pale  straw  color  towards  the 
center,  with  thin  and  irregular  margins ;  sometimes  with  a  central 
light-brown  nucleus ;  at  end  of  10  days  the  deep  colonies  are  still  quite 
small,  of  a  brown  color,  and  opaque. 

In  glycerine-agar  roll-tabes  at  end  of  24  hours  the  deep  colonies  are 
in  the  form  of  a  biconvex  lens,  and  appear  spherical  when  viewed  in 
face  and  biconvex  when  seen  from  the  side  5  they  have  a  straw  color  by 
trausmitted  light,  and  are  bluish  white  by  reflected  light  j  the  sui)er- 
ficial  colonies  are  translucent  with  a  bluish-white  luster. 

On  potato,  at  22°  C,  at  the  end  of  48  hours  there  is  a  thin  dirty  yel- 
low growth  of  limited  extent ;  at  the  end  of  10  days  there  is  a  thin 
gamboge-yellow  layer  and  little  masses  of  the  same  color ;  the  growth 
is  quite  thin,  with  irregular  outlines,  and  is  conflued  to  the  vicinity  of 
the  impfstrich. 

Grows  in  nutrient  agar  containing  0.2  per  cent,  of  hydrochloric  acid 
(1:500)  Thermal-death-point  130^  F.  (about  55°  C). 

Grows  in  agua  coco  without  forming  gas,  and  causes  the  liquid  to 
become  slightly  translucent,  not  milky. 

Not  killed  by  30  minutes  exposure  to  a  temperature  of  10°  F. 

In  its  morphology  this  bacillus  closely  resembles  the  colon  bacillus. 

It  does  not  correspond  with  the -descriptions  of  bacillus  cancida 
(Brieger's  bacillus).  This,  according  to  Fliigge  and  Eisenberg,  forms 
very  characteristic  colonies.  "  Sehr  charakteristic,  in  form  sehr  schon 
gruppierter,  weisslicher,  kouzentrischer  ringe,  die  iinlich  angeordnet 
sind,  wie  die  Schuppen  auf  dem  Eiicken  einer  Schildkrote  "  (Eisenberg). 

I  have  not  seen  anything  answering  to  this  description  in  the  colonies 
of  the  bacillus  under  consideration.  In  order  to  make  the  comparison 
with  Brieger's  bacillus,  I  obtained  from  Dr.  A.  C.  Abbott  a  culture  of 
this  bacillus  from  the  stock  preserved  in  Professor  Welch's  laboratory 
in  Baltimore.    This  also  did  not  present  the  characteristic  colonies 


204  ETIOLOGY    AND    PEEVENTION    OF    YELLOW    FEVER. 

above  described,  uor  did  it  kill  guinea-pigs.  Since  my  return  to  Balti- 
more I  have  again  obtained  a  culture  from  the  same  source,  and  again 
Lave  been  unsuccessful  in  killing  guiuea-pigs  with  it.  A  careful  com- 
parison side  by  side  with  the  bacterium  coli  commune  shows  that  in  its 
characters  of  growth  and  in  its  morphology  this  bacillus  of  Brieger  is 
identical  with  the  bacillus  of  Escherich.  Whether  the  cultures  pre- 
served in  German  laboratories  preserve  their  pathogenic  power  I  am 
unable  to  say. 

The  cultures  of  my  bacillus  cavicida  Havaniensis  which  I  brought  to 
Baltimore  with  me,  upon  being  replanted  after  an  interval  of  3  months, 
failed  to  grow.  I  have  therefore  lost  this  interesting  bacillus  from  my 
collection. 

It  is  very  pathogenic  for  guiuea-pigs,-not  so  pathogenic  for  rabbits. 
This  is  shown  by  the  following  experiments : 

Havana,  June  16,  1689,  12:30  2>-  ™- — Injected  subcutaneoiisly  into  guinea-pig  109,  .3 
minims  of  a  culture  in  agua  coco  from  heart  of  guinea-pig  105  (see  above).  Auimal 
found  dead  next  morning  at  G  o'clock.  Very  slight  subcutaneous  cedenia  near  point 
of  inoculation.     Liver  light  in  color,  contains  a  few  bacilli ;  stomach  hypera;mic. 

June'll,  10  a.  m. — Injected  subcutaneously  into  guinea-pig  110,  4  drops  of  a  culture  iu 
agua  coco  from  heart  of  guinea-pig  No.  105.  Auimal  died  at  10  p.  m.  same  day.  Con- 
siderable subcutaneous  03dema  coutaining  bacillus  re  x.     Bacilli  iu  liver  not  numerous. 

June  17,  10  a.  m. — Injected  subcutaneously  into  guinea  pig  110  4  four  drops  of  a  cul- 
ture in  agua  coco  from  heart  of  guinea-pig  No.  105.  Animal  died  at  10  p.  m.  same 
day.  Considerable  subcutaneous  oedema  containiug  bacillus  x  x.  Bacilli  in  liver  not 
numerous. 

June  17,  10  a.  m. — Injected  into  cavity  of  abdomen  of  guinea-pig  No.  112  I  cubic 
centimetre  culture  bacillus  x  xm  agua  coco.     Died  June  18  at  12  m. 

June  18,  7  a.  m. — Injected  subcutaneously  into  guinea-pig  113,  1  drop  of  bloody 
terum  from  cellular  tissue  of  guinea-pig  llO  (see  above).  Died  at  9  p.  m.,  next  day. 
But  little  subcutaneous  effusion  ;  liver  light  iu  color,  contains  much  fat,  spleen  large. 

June  19,  2:30  jjj.  m. — Injected  subcutaneously  into  guinea-pig  114,  1  drop  of  fluid 
from  anajrobic  culture  in  glycerin  agar  of  bacillus  xx.  June  22,  the  animal  has 
been  very  sick  but  now  appears  better.  June  24,  appears  well.  Died  June  29,  cul- 
sure  from  blood  of  heart,  negative. 

June  23,  10  a.  m. — Injected  subcutaneously  iuto  guinea-pig  118,  one-half  cubic  cen- 
timetre culture  of  bacillus  xx  in  agua  coco  (third  culture  from  heart  of  guinea-pig 
105).   Animal  died  at  9  p.  m.  the  same  day. 

July  17,8  a.  m. — Injected  subcutaneously  into  guinea-pig  155,  one-half  cubic  centi- 
metre culture  of  bacillus  xx  in  agua  coco,  from  agar  stick  culture  two  weeks  old. 
Found  dead  at  6  a.  m.  next  morning.  Extensive  collection  of  bloody  serum  in  walls 
of  abdomen. 

EXPERIMENTS   OJs    RABBITS. 

Havana,  June  20, 1889. — 4j>.  m. — Injected  subcutaneously  into  rabbit  No.  114,  weight 
900  grams,  1  cubic  centimetre  culture  bacillus  xx  in  agua  coco.  June  22,  remains 
well  but  has  a  collection  of  bloody  serum  in  walls  of  abdomen  from  which  a  pure 
culture  of  bacillus  xx  was  obtained.     Died  in  convulsions  at  6  a.  m.  July  23. 

June  23,  18Ji9,  10  a.  m. — Injected  subcutaneously  into  rabbit  115,  one-half  cubic 
centimetre  culture  of  bacillus  xx  in  agua  coco.  Dead  at  6  a.m.  July  25.  Has  had 
a  profuse,  watery  diarrhoea;  no  subcutaneous  oedema. 

June24,  4jj.  m. — Injected  subcutaneously  into  rabbit  No.  117,  1  cubic  ceutimetixs 
culture  bacillus  xx  in  agua  coco.  June  25, 6  a.  m.,  declines  food;  temperature  in 
rectum  106°  F.    This  auimal  recovered. 


ETIOLOGY    AXD    PREVENTION    OF    YELLOW    FEVER.  205 

June  26,0:30  a.m. — Injected  into  cavity  of  abdomen  of  rabbit  118,  1  cubic  centi- 
metre culture  bacillus  xx  in  agua  coco.     Animal  recovered. 

July  7,  9:30  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  123, 1  cubic  centimetre 
culture  of  bacillus  xx  in  agua  coco.     Recovered. 

No.  5.  Bacillus  hepaticus  fortuitus.     (Sternberg.) 

Obtained  in  cultures  from  bloody  serum  in  connective  tissue  of 
guinea-pig  119,  inoculated  with  blood  from  liver  of  case  28, 

An  aerobic,  non-liquefying  bacillus,  not  observed  to  be  motile,  or  to 
form  spores. 

In  gelatine  stick  cultures  does  not  grow  along  line  of  puncture  except 
to  a  slight  extent  near  surface.  On  surface  a  white  mass  is  formed 
about  the  point  of  puncture.     See  Fig.  8,  PL  viii. 

In  gelatine  Esmarch  roll-tubes  forms  spherical  light  brown  colonies, 
homogeneous  or  finel}' granular;  at  end  of  4  days  deep  colonies  are 
lobate,  and  the  superficial  are  like  a  mamma  in  form,  with  striations 
radiating  from  the  center,  and  of  a  dark  brown  color. 

Upon  surface  of  agar  stick  culture  a  soft  and  rather  thin  white  layer 
is  formed  at  end  of  3  days  at  26^  C. 

Upon  the  surface  of  glycerin-agar  the  development  is  quite  rapid, 
nearly  the  entire  surface  being  covered  at  end  of  24  hours  with  a  milk- 
white  growth,  in  incubating  oven  at  35^  C. 

On  potato  at  end  of  48  hours  a  rather  dr^'  and  thick  cream- white 
growth  formed  along  the  impfstrich  at  end  of  48  hours.  The  potato  has 
a  bluish  discoloration  which  afterwards  disappears  ;  at  end  of  2  weeks 
a  rather  thin,  light  brown  semi-fluid  layer  covers  the  entire  surface. 

Abundant  growth  in  agua  coco  at  end  of  24  hours  at  room  tempera- 
ture, without  formation  of  gas. 

Eesembles  bacterium  coli  commune  in  its  morphology,  but  is  dilfer- 
entiated  from  this  bacillus  by  the  fact  that  it  is  strictly  aerobic,  by  its 
colonies  in  gelatine  i^late  cultures,  etc.     See  Fig.  1,  PL  viii. 

Xot  pathogenic  for  rabbits  (single  exx)erimeut  in  which  1  cubic  centi- 
metre of  a  culture  in  agua  coco  was  injected  into  cavity  of  abdomen). 

No.  6.  Bacillus  iutestinus  motilis.  (Sternberg.) 

Obtained  in  cultures  from  the  contents  of  the  intestine  of  yellow-fever 
cadavers  in  Havana,  1889. 

A  small,  actively  motile,  non-Uquefying  bacillus  of  the  "  colon  group." 
A  facultative  ayiae'rohic.  In  gelatine  stick  cultures  pale  straw-colored 
colonies  along  line  of  puncture  to  bottom,  and  a  rather  thin  translucent 
white  layer  upon  surface.  Sometimes  a  nebulous  outgrowth  occurs 
from  the  line  of  puncture  and  tufted  outlying  colonies  are  formed 
throughout  the  gelatine  ;  at  other  times,  in  old  cultures,  a  few  feathery 
tufts  sprout  out  from  the  line  of  puncture. 

In  gelatine  roll-tubes,  at  end  of  24  hours  at  27^  C.  the  deep  colonies 
are  spherical  and  homogeneous  and  of  a  pale  straw  color  ;  superficial 
colonies  are  like  little  drops  of  water,  of  a  pale  brown  color. 

Grows  in  agua  coco  without  forming  gas, 


206  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

On  potato  the  growth  is  rather  thin  and  of  a  pale  yellow  color,  not 
extending  far  from  line  of  impfstricb. 

In  its  morphology  this  bacillus  resembles  the  "colon  bacillus  "of 
Escherich,  but  it  is  distinguished  from  it  by  its  active  movements,  its 
colonies  in  gelatine  roll-tubes,  etc.     See  Fig.  2,  PI.  viii. 

Kot  pathogenic  for  guinea-pigs;  not  tested  upon  other  animals. 
No.  7.  Bacillus  cavia  fortuitus.     (Sternberg.) 

Obtained  in  pure  culture  from  liver  of  guinea-pig  134,  inoculated 
subcutaneously  with  2  minims  of  material  from  liver  of  case  27,  pre- 
served 48  hours  in  an  antiseptic  wrapping. 

An  actively  motile,  non-liquefying  bacillus.    Facultative  anaerobic. 

In  gelatine  stick  cultures  there  is  a  scanty  growth  on  surface  at. 
point  of  puncture ;  growth  to  bottom  of  stick,  where  the  colonies  ar& 
spherical,  translucent,  straw-colored  and  pearl  like  by  reflected  lights 
Colonies  in  gelatine  roll-tube  at  end  of  three  days,  small^  spherical,, 
light  brown  in  color  at  first,  later  opaque,  sometimes  with  an  opaqn& 
granular  central  portion  surrounded  by  a  transparent  zone. 

Growth  on  potato  at  end  of  a  week  in  form  of  small  dirty  yeUow 
masses. 

Does  not  form  gas  in  agua  coco. 

The  morphology  of  this  bacillus  is  shown  by  my  photomicrograiih. 
Fig.  3,  PI.  VIII. 

A  culture  in  agua  coco  (1  cubic  centimetre)  injected  subcutaneously 
into  guinea-pig  138  gave  a  negative  result.  JSfo  further  experiments 
made  with  reference  to  pathogenic  power. 

No.  8.  Bacillus  caniculacida.     (Koch.) 

I  obtained  the  bacillus  of  rabbit  septicaemia  in  Havana  under  the 
following  circumstances:  A  guinea-pig  was  inoculated  subcutaneously 
on  the  31st  of  July  with  2  minims  of  material  from  the  liver  of  case 
29,  kept  48  hours' in  an  antiseptic  wrapping.  The  animal  died  at  the 
end  of  26  hours  and  1  cubic  centimetre  of  a  culture  in  blood  serum 
from  its  liver  was  injected  on  the  6th  of  August  beneath  the  skin  of  a 
rabbit.  The  animal  died  at  the  end  of  22  hours,  and  a  culture  of  the 
bacillus  of  rabbit  septicaemia  was  obtained  from  its  liver.  Two  drops 
of  blood  from  the  heart  of  the  above  rabbit  injected  beneath  the  skin 
of  another  rabbit  caused  its  death  at  the  end  of  20  hours.  Its  blood 
contained  the  same  bacillus. 

On  the  10th  of  August  another  rabbit  was  inoculated  subcutaneously 
with  3  minims  of  material  from  the  liver  of  case  31.  This  animal  died 
in  convulsions  at  the  end  of  48  hours,  and  the  bacillus  of  rabbit  septi- 
ciemia  was  recovered  from  its  liver. 

On  the  11th  of  August  at  3  p.  m.  one-half  cubic  centimetre  of  a  cul- 
ture of  this  bacillus  in  veal  broth  was  injected  beneath  the  skin  of 
another  rabbit.  This  animal  died  at  9  p.  m.  the  same  evening  and  the 
bacillus  was  found  in  abundance  in  its  blood, 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  207 

Having  in  the  rabbit  a  test  for  the  presence  of  this  bacillus,  and 
having  found  it  in  two  cases,  I  continued  the  search  for  it  in  some  sub- 
sequent autopsies  as  follows : 

August  12,  1:30  J),  m. — Injected  Ijeneath  the  skin  of  rabbit  No.  164,  5  minims  of  liver 
pulp  from  case  32.     Result  negative. 

August  13,  12:30  p.vi. — Injected  subcutanenusly  into  rabbit  169,  4  minims  of  liver 
pulp  from  case  33.     Result  negative. 

August  lo,  1:30 ji-m. — Injected  subcutaneously  into  rabbit  171,  1  cubic  centimetre 
of  material,  principally  blood,  from  case  35.     Result  negative. 

August  17,  9:30  a.  m. — Injected  subcutaneously  into  rabbit  176,  4  minims  from  liver 
of  case  35,  kept  48  hours  iu  antiseptic  wrapping,  material  contains  bacillns  N  and 
other  bacilli.  Animal  found  dead  at  6  a.  m.  August  21.  Bacillns  of  rabbit  septi- 
caemia not  present.     A  motile  bacillus  obtained  in  cultures  from  liver. 

August  Vd,l:3Q. — Injected  subcutaneously  into  rabbit  178,  one-half  cubic  centi- 
metre crushed  parenchyma  from  liver  of  case  36.     Result  negative. 

August  21,  10:30  jj.  m. — Injected  subcutaneously  into  rabbit  183,  2  minims  mateiial 
from  liver  of  case  37.     Result  negative. 

August22,  1:45 j>.  m. — Injected  subcntaneouslj-  into  rabbit  184,  1  cubic  ccnitmetre 
blood  and  crushed  jjarenchyma  from  liver  of  case  38.     Result  negative. 

These  experiments  suffice  to  show  that  the  presence  of  this  widely 
distributed  pathogenic  bacillus  in  two  cases  was  accidental,  and  of  no 
significance  so  far  as  the  etiology  of  yellow  fever  is  concerned. 

No.  9.  Bacillus  Havaniensis  (Sternberg). 

This  is  an  aerobic,  cliromogenk  bacillus  (micrococcus!)  whicb  I  ob- 
tained in  my  cultures  from  the  kidney  in  a  single  case,  in  Havana,  in 
1888.  It  is  extremely  small,  as  will  be  seen  by  reference  to  my  photo- 
micrograph, Fig.  1,  PI.  IX,  and  should  perhaps  be  described  as  a  micro- 
coccus. 

It  is  not  motile,  and,  so  far  as  my  observations  go,  does  not  form 
spores. 

It  does  not  liquefy  gelatine,  but  grows  upon  the  surface  of  flesh  pep- 
tone-gelatine as  an  opaque,  brick  red  or  carmine  layer,  which  develops 
slowly  and  extends  very  gradually  from  the  point  of  inoculation.  There 
is  a  scanty  development  near  the  surface  in  gelatine  stick  cultures,  but 
the  characteristic  color  is  only  formed  upon  the  surface  where  there  is 
free  access  of  oxygen. 

On  nutrient  agar  the  growth  is  slow  but  continuous,  forming  at  the 
end  of  10  days  at  the  room  temperature  a  heaped-up  carmine  mass. 

Frequently  this  bacillus  fails  to  grow  upon  the  surface  of  cooked 
potato,  perhaps  because  of  an  acid  reaction  of  the  potato.  But  some- 
times it  grows  as  it  does  on  nutrient  agar,  forming  a  thick  irregular 
mass  of  a  bright  carmine  color,  as  seen  in  Fig.  1,  PI.  xix.  Dr.  Kemp, 
of  the  Hoagland  laboratory,  who  succeeded  in  obtaining  a  culture  on 
potato  after  I  had  failed,  thinks  that  it  grows  more  readily  on  cooked 
potato  which  has  been  kept  for  some  time  and  has  become  dry. 

In  gelatine  roll-tubes  the  colonies  are  small,  spherical,  translucent, 
and  of  a  beautiful  blood-red  color. 

I  have  a  variety  of  this  bacillus  in  cultivation  which  has  scarcely  any 


208  ETIOLOGY   AND    PREVENTION    OF    YELLOW   FEVER. 

color— a  trace  of  pink  only.  This  is  from  a  pure  culture  which  had  the 
usual  deep  carmine  color  and  which  I  kept  for  a  year  in  a  herraatically 
sealed  glass  tube.  Upon  replanting  it  at  the  end  of  this  time  in  nutri- 
ent agar  it  grew,  hut  has  since  been  almost  without  color.  The  growth 
is  also  less  abundant.  This  bacillus  is  not  pathogenic  for  guinea  pigs.  I 
have  not  tested  it  upon  other  animals. 

No.  10.   Baccillus  vacuolosis  (Sternberg). 

I  obtained  this  bacillus  in  one  case  in  my  cultures  from  the  intestine, 
in  one  case  from  the  stomach,  and  in  one  case  a  few  colonies  were 
obtained  in  cultures  from  the  kidneys. 

The  morphology  is  shown  by  my  photomicrograph,  Fig.  3,  PI.  ix.  It 
varies  considerably  in  its  dimensions,  especially  in  old  cultures,  in 
which  a  variety  of  involution  forms  are  encountered.  The  rods  are 
often  more  or  less  curved  and  may  grow  out  into  long-jointed  iilameuts. 
They  present  the  appearance  of  containing  numerous  vacuoles  in  the 
protoplasm;  these  are  not  spores,  but  this  bacillus  forms,  under  certain 
circumstances,  large  oval  spores.  It  is  sometimes  motile,  the  move- 
ments being  slowly  progressive,  with  a  to  and  fro  movement,  as  if  pro- 
pelled by  a  flagellum.  It  liquefies  gelatine  slowly  in  cup  shape,  the  lique- 
fied gelatine  being  quite  viscid  with  a  cream-white  layer  of  bacilli  on 
the  surface.     It  does  not  grow  in  an  acid  medium. 

In  nutrient  agar  the  growth  along  the  line  of  puncture  is  scanty ;  on 
the  surface  it  forms  a  cream-white  layer  and  the  bacilli  grow  out  into 
long-jointed  filaments. 

On  potato  it  forms  a  thin  cream-white  layer. 

Not  pathogenic  for  rabbits  ;  not  tested  upon  other  animals. 

ISTo.  11.  Bacillus  fluorescens  liquefaciens. 

This  bacillus  I  first  encountered  in  Havana,  in  1888,  in  cultures  from 
the  spleen,  stomach,  and  fluid  in  the  peritoneal  cavity  of  case  2.  In  my 
researches  in  Decatur,  in  the  autumn  of  the  same  year,  I  obtained  it  in 
a  number  of  cases  in  ray  cultures  from  the  feces  of  yellow-fever  patients. 

It  is  a  motile,  liquefyirig  bacillus,  which  forms  a  greenish  pigment  and 
gives  to  the  liquefied  gelatine  a  fluorescent  greenish  color  (see  Fig.  2, 
PI.  XXI).  A  thick  white  deposit,  consisting  of  bacilli,  settles  to  the  floor 
of  the  liquefied  gelatine. 

On  potato,  at  the  end  of  two  weeks,  at  the  room  temperature  a  rather 
thin  pale  brown  layer  covers  the  greater  part  of  the  surface;  this  has  a 
varnished  shining  appearance  as  seen  in  Fig.  1,  PI.  xxi. 

This  bacillus  is  about  0.8  /t  in  diauieter  and  four  or  five  times  as  long 
as  broad.  It  is  frequently  joined  in  pairs,  as  seen  in  my  photomicro- 
graph, Fig.  2,  PI.  ix. 

I  have  made  no  experiments  with  reference  to  its  pathogenic  power, 
having  lost  my  culture  of  it  during  my  absence  in  Havana  last  sum- 
mer. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER.  209 

No.  12.  Bacillus  pyocyanus  (Gessard). 

Obtained  from  the  liver  of  case  28,  Havana,  1889,  and  from  the 
feces  of  a  case  in  Decatur,  in  3888;  a  liquefying  bacillus  which  forms 
a  green  pigment  and  appears  to  be  identical  with  the  bacillus  pyocya- 
nus. 

It  is  actively  motile.  Its  morphology  is  shown  in  my  photomicro- 
graph, Fig.  1,  PI.  X,  and  its  growth  in  gelatine  by  Fig.  2,  PI.  ix. 

Upon  potato  a  chocolate-colored  layer  is  formed,  as  shown  in  Fig.  3, 
PI.  XIX.  The  potato  sometimes  acquires  a  green  color  and  sometimes 
does  not. 

Agar  cultures  acquire  a  beautiful  fluorescent  green  color,  which  pen- 
etrates the  medium  from  the  surface,  where  the  pigment  is  formed  in 
presence  of  oxygen.  Old  agar  cultures  acquire  an  olive-brown  color. 
The  growth  upon  the  surface  of  agar  is  abundant,  of  a  white  color  tinted 
slightly  green,  and  is  quite  viscid. 

A  thin  mycoderma  forms  upon  the  surface  of  the  liquefied  gelatine  in 
gelatine  cultures,  and  it  is  here  that  the  pigment  is  formed. 

Young  colonies  in  gelatine  roll-tubes  are  coarsely  granular,  light- 
brown  in  color,  and  are  sometimes  surrounded  by  a  transparent  ruffle- 
like margin,  as  shown  in  Fig.  3,  PI.  x.  Later  liqueficatidn  occurs,  as  is 
shown  in  Fig.  4  of  the  same  plate. 

This  bacillus  is  pathogenic  for  guinea-pigs  and  rabbits,  as  shown  by 
the  following  experiments : 

Baltimore,  March  13,  1890,  10  a,  m. — Injected  suljcutaneously  into  guinea-pif  209 
one-half  cubic  centimetre  liquefied  gelatine-culture  of  bacillus,  12.  Found  dead  next 
morning  at  8  o'clock  ;  bacillus  pyocyanus  recovered  from  blood  of  heart. 

March  10,  9:30  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  1  cubic  centimetre 
liquified  gelatine-culture  of  bacillus  12.  Animal  died  without  convulsions  at  1 
o'clock  the  same  day. 

March  10, 9:30  a.  m. — Injected  snbcutaneously  into  rabbit  258,  weight  2,075  grammes 

I  cubic  centimetre  liquefied  gelatine-culture  of  bacillus  12.  Animal  recovered,  and 
on  the  22d  of  March  received  in  the  cavity  of  the  abdomen  2  cubic  centimetres 
liquefied  gelatine-culture  of  the  same  bacillus.  Result  negative.  (Protected  by  first 
inoculation.) 

March  13,  10  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  No.  262,  weight  720 
grammes,  one-half  cubic  centimetre  liquefied  gelatine-culture  of  bacillus  12.  Ani- 
mal found  dead  next  morning  at  8  o'clock.  Bacillus  recovered  in  pure  culture  from 
liver. 

March  13,  10  a.  m.— Injected  subcutaneously  into  rabbit  No.  263,  weight  650 
grammes,  one-half  cubic  centimetre  liquefied  gelatine-culture  of  bacillus  12.  Animal 
found  dead  next  morning  at  8  o'clock.     Bacillus  recovered  in  pure  culture  from  liver. 

March  15,  9:30  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  No.  274,  weight  .505 
grammes,  1  cubic  centimetre  sterile  culture  of  bacillus  12.    Result  negative.    March  22, 

II  a.  m.,  injected  into  cavity  of  abdomen  of  the  same  rabbit  2  cubic  centimetres  lique- 
fied gelatine-culture  of  bacillus  12.  Animal  remained  in  good  health.  Protection 
by  injection  of  a  sterile  culture. 

No.  13.  Bacillus  liquefaciens  commune.    (My  bacillus  o,  Decatur,  1888). 

This  bacillus  was  present,  in  comparatively  small  numbers,  in  about 
half  the  cases,  in  my  cultures  from  the  feces  of  yellow  fever  patients, 
made  at  Decatur,  Ala.,  in  the  autumn  of  1888. 
4067 14 


210     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 

It  is  an  actively  motile,  liquefying  bacillus. 

In  its  morphology  it  resembles  the  coIod  bacillus,  being  a  short  x'od 
with  rounded  ends,  three  or  four  times  as  long  as  broad.  See  my  pho- 
tomicrograph, Fig.  2,  PI.  X. 

In  gelatine  stick  cultures  liquefaction  occurs  rapidly  in  the  form  of  a 
purse,  as  is  shown  in  Fig.  6,  PI.  x. 

Growth  occurs  at  a  comijaratively  low  temperature;  a  culture  ex- 
posed in  an  attic  room  in  Baltimore  in  the  month  of  January  showed 
decided  development  with  liquefaction  of  the  gelatine. 

On  potato  the  growth  at  the  end  of  two  weeks  is  of  pinkish  color, 
and  more  or  less  irregular  and  corrugated,  as  shown  in  Fig.  3,  PI.  xxi. 

This  bacillus  grows  readily  in  a  gelatine  medium  containing  0.2  per 
cent  of  hydrochloric  acid. 

The  following  experiments  show  that  it  is  not  decidedly  pathogenic 
for  rabbits : 

Baltimore,  December  5,  1888. — Injected  siibcntaneously  into  rabbit  No,  59,  weight 
872  grammes,  2  cubic  centimeters  liquefied  gelatine-culture  bacillus  o.  Tlie  animal 
had  some  cellulitis  at  point  of  inoculation,  and  an  abscess,  but  recovered. 

Baltimore,  December  5,  1888. — Injected  subcutaneously  into  rabbit  No,  CO,  weight  545 
grammes,  one-fourtb  cubic  centimetre  liquefied  gelatine-culture  of  bacillus  o.  Some 
cellulitis  at  point  of  inoculation  ;  recovered. 

Baltimore,  December  12,  1888. — Injected  into  cavity  of  abdomen  of  rabbit  64,  weight 
715  grammes,  2^  cubic  centimeters  liquefied  gelatine-culture  of  bacillus  o.  Abscess 
formed  at  point  of  inoculation,  but  animal  recovered. 

No.  14.  Bacillus  subtilis.     (Ehrenberg.) 

In  my  autopsy  No.  12,  made  at  Pecatur,  Ala.,  in  the  autumn  of  1888, 
I  obtained  in  my  cultures  from  the  stomach  and  intestine  a  motile,  lique- 
fying bacillus,  which  proved  to  have  all  the  characters  of  the  widely 
distributed  species  known  under  the  above  name.  In  Havana,  in  1889, 
I  obtained  the  same  bacillus  in  cultures  from  the  surface  of  the  body  of 
yellow-fever  patients  in  the  Civil  Hospital.  This  is  a  large  bacillus, 
which  grows  out  into  long-jointed  filaments  and  forms  large  oval  spores. 
It  liquefies  gelatine  quite  rapidly  in  the  form  of  a  purse.  On  potato, 
at  the  end  of  10  days  a  rather  dry,  dirty-white  layer  covers  the  entire 
surface;  this  is  made  up  of  free  spores  and  spore-bearing  filaments. 

No.  15.  Bacillus  subtilis  similis  (Sternberg). 

This  is  a  liquefying,  motile  bacillus,  which  forms  large  oval  spores,  and 
resembles  bacillus  subtilis.  I  obtained  it  in  cultures  from  the  liver  of 
case  22,  Havana,  1889.     It  is  2b  facultative  anaerohic. 

In  gelatine  roll-tubes  the  young  colonies  at  the  end  of  36  hours,  at 
room  temperature,  are  spherical,  finely  granular,  and  pearl-like  by 
reflected  light.  The  superficial  colonies  at  the  same  time  have  com- 
menced to  liquefy  and  have  a  granular  white  mass  at  the  center  sur- 
rounded by  liquefied  gelatine.     See  Fig,  2,  PI.  xi. 

The  morphology  is  shown  by  my  photomicrograph.  Fig.  1,  PI.  xi,  in 
which  the  oval  spores  are  seen  in  the  interior  of  some  of  the  rods.  This 
bacillus  does  not  liquefy  gelatine  as  rapidly  as  bacillus  subtilis.    In  a 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  211 

gelatine  stick  culture  at  70°  F.  at  the  end  of  10  days  the  upper  half  of 
the  gelatine  was  liquefied  and  small  pearl-like  colonies  were  scattered 
along  the  line  of  puncture  below.  On  the  floor  of  the  liquefied  gelatine 
was  a  floculent  white  deposit  and  a  thin  myeoderma  on  the  surface. 
The  bacilli  in  recent  cultures  have  a  slow  to  and  fro  progressive  move- 
ment, as  if  propelled  by  a  flagellum. 

On  potato,  at  86°  F.,  a  dry,  yellowish- white  layer  the  size  of  a  dime 
was  formed  at  the  end  of  48  hours.  In  this  culture  the  bacillus  had 
grown  out  into  long  jointed  filaments  containing  spores.  In  Baltimore 
at  a  later  date  tbe  growth  on  potato  was  a  dry,  white  growth  of  limited 
extent  at  the  end  of  5  days. 

On  the  surface  of  nutrient  agar  a  thick  cream-white  layer  is  formed 
at  the  end  of  4  or  5  days  at  the  room  temperature.  Along  tlie  upper 
IDortion  of  the  line  of  puncture  there  is  a  branching  growth.  In  an 
agar  culture  of  12  days  the  growth  upon  the  surface  contained  but  few 
spores,  and  variously  contorted  involution  forms  of  the  bacillus  were 
present. 

I  have  made  but  a  single  experiment  with  reference  to  the  pathogenic 
power  of  this  bacillus,  as  follows: 

Baltimore,  March  1,  1890. — Injected  into  the  cavity  of  the  abdomen  of  rabbit  No. 
239,  weight  1,400  grammes,  one-half  a  cubic  centimetre,  liquefied  gelatine-culture  of 
bacillus  15.  March  10,  weight  1,250  grammes ;  animal  in  apparent  good  health,  but 
has  had  a  large  ulcer  at  the  point  of  injection. 

No.  16.  Bacillus  intestinus  liquefaciens  (Sternberg). 

Obtained  from  the  intestine  of  case  27,  Havana,  1889. 

This  is  a  motile,  liquefying  bacillus. 

In  gelatine  stick-cultures  the  upper  portion  of  the  gelatine  is  lique- 
fied, and  pale  straw-colored  colonies  are  scattered  along  the  line  of 
puncture  below. 

Upon  potato  the  growth  is  rather  thin  and  of  a  pale  yellow  color. 

In  its  7norpliology,  this  bacillus  presents  nothing  characteristic;  it 
probably  belongs  to  the  "proteus"  group.  The  rods  are  about  O.Sjj.  in 
diameter,  and  two  or  three  times  as  long  as  broad.     See  Fig.  4,  PI. 

XI. 

No.  17.  Bacillus  filiformis  (Sternberg). 

Obtained  in  anaerobic  cultures  in  glycerine-agar  from  liver  of  case 
36,  Havana,  1889. 

A  facultative  anae'rohic. 

No  motion  observed ;  does  not  form  spores. 

Colonies  in  anaerobic  glycerine-agar  tube,  spherical  or  irregular  in 
outline,  straw  color  or  pale  brown,  white  and  opaque  by  reflected 
light;  superficial  colonies  are  thin  and  translucent,  and  have  a  bluish 
luster  by  reflected  light;  later  they  appear  as  cream-like,  irregular 
masses. 

Kg  growth  in  agua  coco ;  scanty,  milk-white  growth  on  surface  of 
nutrient  agar  and  opaque,  branching  growth  along  line  of  puncture. 


212     ETIOLOGY  AND  PEEVENTION  OF  YELLOW  FEVER. 

No  growth  upon  potato. 

Scanty  growth  in  gelatine  stick-culture  along  line  of  puncture,  none 
on  surface,  Fig.  6,  PI.  xiii. 

G-rows  in  neutral  bouillon,  causing  a  slight  opalescence,  and  later  a 
scanty  white  sediment. 

In  my  anaerobic  cultures  made  in  Havana  this  bacillus  was  shorter 
and  thicker  than  it  appears  in  my  photomicrograph,  Fig.  1,  PI.  xiii. 
In  old  agar-cultures  the  bacilli  are  very  much  attenuated  and  a^jpear 
as  long  homogeneous  filaments  of  various  dimensions. 

Not  pathogenic  for  rabbits  or  guinea-pigs. 

No.  18.  Bacillus  cadaveris  (Sternberg.)     (Bacillus  N,  Havana,  1889.) 

This  is  a  large  anaerobic  bacillus,  which  was  the  most  constant  and 
abundant  microorganism  found  iu  pieces  of  liver  and  kidney  kept  for 
48  hours  in  an  antiseptic  wrapping.  It  was  also  present,  in  two  cases, 
in  smear  i)reparations  made  from  fresh  liver  tissue.  Since  my  return 
from  Havana  I  have  found  it  in  pieces  of  liver  j)re8erved  in  the  same 
way  from  my  comparative  autopsies. 

Fig.  1,  PI.  XII,  is  a  photomicrograph  from  a  smear  preparation  made 
from  the  liver  of  Case  18  (Havana,  1889),  preserved  for  48  hours  in  an 
antiseptic  wrapping.  Other  bacilli  are  associated  with  the  large  anae- 
robic bacillus,  but  this  is  the  most  conspicuous  and  most  abundant. 
Invariably  the  tissue  contaicing  it  has  a  very  acid  reaction  ;  it  is  rather 
soft  but  preserves  its  fresh  appearance  and  havS  not  a  putrefactive  odor. 

This  bacillus  is  usually  about  twice  as  long  as  broad,  but  may  grow 
out  into  rather  long  threads. 

The  ends  of  the  rods  are  square  or  slightly  rounded.  It  is  motionless 
and  so  far  as  my  observations  go  does  not  form  spores.  In  my  x)hoto- 
micrographs  it  is  associated  with  a  small  coccus  in  pairs,  which  I  iso- 
lated in  pure  cultures  and  have  studied  separately  (see  p.  218). 

Bacillus  cadaveris  is  a  strict  a  naerobic  and  is  difficult  to  cultivate. 
I  have  succeeded  best  with  nutrient  agar  containing  5  per  cent,  of 
glycerine,  removing  the  oxygen  thoroughly  by  passing  a  stream  of 
hydrogen  through  the  liquefied  medium.  The  colonies  in  a  glycerine 
agar  roll-tube  (containing  hydrogen  and  hermetically  sealed)  are 
opaque,  irregular  in  outline,  granular,  and  of  a  white  color  by  reflected 
light.  The  culture  medium  acquires  an  acid  reaction  as  a  result  of  the 
development  of  the  bacillus. 

An  account  has  already  been  given  of  the  pathogenic  power  of  liver 
tissue  containing  this  bacillus  (see  p.  127).  My  experiments  with  pure 
cultures  are  given  below  : 

Havana,  May  19,  1889.— Injected  into  cavity  of  abdomen  of  rabbit  106  bacillus  N 
from  culture  in  glycerine  agar,  suspended  in  1  cubic  centimetre  of  veal  broth.  Eesult, 
negative. 

Havana,  May  16,  1889,  10  a.  m.— lujected  subcutaneously  into  guinea-pig  No.  44,  3 
minims  of  liquid  from  agar-culture  of  bacillus  N.  The  animal  was  found  dead  the 
next  morning  at  6  o'clock.     Extensive  subcutaneous  cedema  containing  bacillus  N. 


ETIOLOGY    AND    PREVENTION    OF    YELLOW   FEVER.  213 

Havana,  May  17,  1889,  3  2:>.  m.— lujected  subcntaneonsly  into  gninea-pig  48,  3  min- 
ims of  liquid  from  agar-culture  of  bacillus  N.  Animal  found  dead  morning  of  May- 
Si.     No  subcutaneous  cedema ;  no  bacilli  in  blood. 

Havana,  June  12,  1889,  9:30  a.  m. — Injected  subcutaneously  into  guinea-pig  97, -5  min- 
ims anaerobic  culture  in  glycerine-agar  of  bacillus  N.  Animal  died  at  10  p.  m.,  June 
14.  No  local  cedema  ;  abdominal  viscera  normal  in  appearance ;  no  microorganisms 
in  blood. 

Havana,  June  12,  1889,  9:30  a.  m. — Injected  subcutaneously  into  guinea-pig  98,  10 
minims  anaerobic  culture  bacillus  N  in  glycerine-agar.     Result,  negative. 

I  regret  that  these  experiments  were  not  extended,  inasmuch  as  they 
give  a  somewhat  contradictory  result.  They  show,  however,  that  pure 
cultures  of  this  bacillus  are  not  as  pathogenic  for  guinea-pigs  as  is  the 
material  from  yellow  fever  livers  kept  in  an  antiseptic  wrapping  for  48 
hours  in  which  bacillus  N  is  associated  with  other  microorganisms. 
As  none  of  the  microorganisms  isolated  from  such  material  have  shown 
a  virulence  corresponding  with  that  of  the  material  itself,  lam  disposed 
to  think  that  the  local  inflammatory  oedema  which  results,  esi:)ecially  in 
guinea-pigs,  from  injecting  it  beneath  the  skin  depends  upon  the  pres- 
ence of  the  toxic  ptomaines  i)resent,  in  connection  with  the  microor- 
ganisms which  produce  these  ptomaines. 

No.  19.  Bacillus  cadaveris  grandis  (Sternberg). 

This  is  a  large  anaerobic  bacillus,  which  was  occasionally  present  in 
the  fragments  of  liver,  etc.,  kept  for 
48  hours  in  an  antiseptic  wrapping. 
I  have  encountered  it  still  more  fre- 
quently in  liver  tissue  preserved  in 
the  same  way  from  my  comparative 
autopsies.  I  have  not  obtained  it 
in  my  cultures.  The  morphology  is 
shown  in  Fig.  22,  in  which  the  am- 
plification is  about  1,000  diameters. 

The  rods  have  a  rounded  extrem. 
ity  and  usually  contain  a  large  oval 
spore  at  one  end  ;  sometimes  there 
is  a  spore  at  each  end. 

No.  20.  Clostridium  cadaveris  (Sternberg).     (Bacillus  T,  Havana,  1889.) 

This  is  ?[,  facultative  anaerobic,  non-motile  bacillus,  which  I  obtained  in 
anaerobic  cultures  in  glycerine-agar  associated  with  Bacillus  cadaveri- 
nus,  from  a  fragment  of  liver  preserved  in  an  antiseptic  wrapping. 

It  is  a  Clostridium, forming  large  oval  spores  in  the  center  of  the  rods, 
but  these  spores  are  only  developed  in  free  contact  with  oxygen.  In 
agar  stick-cultures  they  are  formed  upon  the  surface,  while  along  the 
line  of  puncture  the  rods  are  longer  and  may  grow  out  into  long  fila- 
ments as  seen  in  Fig.  4,  PI.  xii. 
The  rods  are  about  Ipi  in  diameter  and  o  to  20  or  more  in  length.  ' 
In  gelatine  stick-cultures  the  growth  upon  the  surface  is  very  scanty 


214  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

and  thin,  of  a  cream  white  color;  at  the  bottom  of  the  line  of  puncture 
large,  transluscent,  straw-colored  colonies  are  formed. 

In  agar  stick-cultures  the  growth  along  the  line  of  puncture  is  opaque 
and  upon  the  surface  forms  a  thin  whitish  layer. 

In  bouillon  cultures  long  motionless  filaments  are  formed  and  the 
bouillon  is  slightly  clouded. 

But  a  single  experiment  has  been  made  to  test  the  i^athogenic  power 
of  this  bacillus.  One  cubic  centimetre  of  a  bouillon  culture  injected 
beneath  the  skin  of  a  rabbit  gave  a  negative  result. 

No.  21.  Bacillus  anaerobicus  liquefaciens  (Sternberg). 

Obtained  in  anaerobic  cultures  from  the  contents  of  the  intestine. 
Case  15  (Havana,  1889). 

A  strictly  cmaerobic,  non-motile  bacillus. 

In  anaerobic  gelatine  roll-tubes  it  forms  granular  white  colonies,  sur- 
rounded by  liquefied  gelatine.  No  growth  in  aerobic  culture  in  flesh- 
peptone- gelatine. 

In  a  long  stick  culture  in  nutrient  agar  it  grows  along  the  line  of 
puncture  except  near  the  surface. 

A  retained  culture  in  agar^  of  May  15,  failed  to  grow  when  replanted, 
in  Baltimore,  in  November. 

In  its  morphology  this  bacillus  is  a  slender  rod  about  0.6 pi  in  diam- 
eter and  three  to  five  times  as  long  as  broad;  the  rods  are  often  joined 
in  i)airs  and  may  grow  out  into  threads.     It  forms  spores. 

No  experiments  as  to  pathogenic  power. 

No.  22.  Bacillus  renalis  fortuitus  (Sternberg.) 

Obtained  in  cultures  from  kidney.     Case  18  (Havana,  1889). 

A  facultative  anaeroMc. — Not  observed  to  be  motile.  Does  not  liquefy 
gelatine.  No  growth  on  potato.  Suj)erficial  colonies  in  agar  roll-tube, 
spherical,  cream  white.  Culture  of  May  16th  failed  to  grow  when  re- 
planted in  Baltimore  in  November.  The  morphology  is  shown  by  my 
photomicrograph.    Fig.  4,  PI.  xiy. 

No.  23.  Bacillus  Martinez  (Sternberg;. 

Obtained  from  liver,  case  29,  48  hours  in  antiseptic  wrapping. 

A  short  oval  bacillus,  see  Fig.  2,  PI.  xiii.  Not  motile ;  does  not 
liquefy  gelatine. 

Facultative  anaerobic. 

Growth  to  bottom  of  puncture  in  stick-culture  in  glycerine-?.gar, 
scanty  growth  on  surface. 

In  glycerine-agar  roll-tube  a  thin,  siireading,  white  growth.  In  gela- 
tine stick-culture  thin  and  scanty  growth  on  surface  and  large,  spher- 
ical, translucent  colonies  below.  Superficial  colonies  in  gelatine  roll- 
tubes  like  a  mamma,  with  mosaic  markings  on  surface,  see  Fig.  4,  PI. 
XIII.    Deep  colonies  spherical  and  translucenc. 

Not  pathogenic  for  rabbits.     (Single  experiment.) 


ETIOLOGY   AND    PREVENTION    OF    YELLOW    FEVER.  215 

No.  24.  Bacillus luteus  commune  (Sternberg). 

Obtained  from  liver,  case  27,  48  hours  in  antiseptic  wrapping.  A 
single  colony,  probably  accidental. 

Aerobic  ;  not  motile  ;  does  not  liquefy.  Upoii  the  surface  of  agar  cul- 
tures a  dry  yellow  mass.  Deep  colonies  in  gelatine  roll-tubes  irregu- 
lar in  outline,  granular  and  yellow  in  color ;  superficial  colonies  have 
an  ojjaque  yellow  center  and  a  thin,  irregular,  translucent  margin. 

For  morphology,  see  photomicrograph,    Fig.  5,  PI.  xv. 

No.  25.  Bacillus  L^  Havana,  1889. 

Obtained  in  gelatine  cultures  from  feces  of  yellow-fever  case  in  Ha- 
vana, 1889. 

An  actively  motile,  liquefying  bacillus.  In  gelatine  stick  cultures  at 
end  of  4  days  at  28°  0.  the  gelatine  is  liquefied  above  and  is  milky  in 
appearance ;  at  end  of  9  days  the  liquefied  gelatine  is  clouded  through- 
out, has  a  greenish  tint  near  surface,  and  a  heavy  white  deposit  below. 

On  potato  at  end  of  5  days  a  pinkish  white  growth,  rather  thick,  with 
irregular  margins ;  contains  gas  bubbles. 

In  nutrient  agar  a  milk-white  growth  on  surface,  and  rather  scanty, 
opaque  growth  along  line  of  puncture* 

For  morphology,  see  Fig.  4,  PI.  xv. 

No.  26.  Bacillus  C,  Havana,  1889. 

Obtained  in  gelatine  cultures  from  kidney,  case  18.  An  actively 
motile,  liquefying  bacillus;  see  Fig.  3,  PL  xv. 

No.  27.  Bacillus  K,  Havana,  1889. 

Obtained  in  culture  from  surface  of  the  body  of  case  in  civil  hospital, 
Havana. 

A  motile,  liquefying  bacillus.  Liquefies  gelatine  in  cup-shape  near 
surface;  growth  to  bottom  of  line  of  puncture  consisting  of  small,  trans- 
lucent colonies ;  liquefied  gelatine  very  slightly  clouded,  almost  trans- 
parent. 

No  growth  on  potato. 

In  nutrient  agar  scanty  yellowish-brown  growth  on  surface,  and 
branching  growth  along  line  of  puncture. 

For  morphology,  see  Fig.  2,  PI.  xv. 

No.  28.     Bacillus  Havaniensis  liquefaciens.     (Bac.  1.) 

Obtained  in  cultures  from  the  surface  of  the  body  of  patients  in  tlie 
civil  hospital,  Havana,  1889. 

A  motile,  liquefying  bacillus,  with  round  ends ;  grows  out  into  long 
threads.    No  formation  of  spores  observed. 

In  gelatine  stick-cultures  liquefaction  occurs  all  along  the  line  of 
puncture,  as  shown  in  Fig.  8,  PI.  xiv.  The  liquefied  gelatine  at  end  of 
4  days,  at  22°  C,  is  slightly  clouded  throughout ;  in  old  cultures  the 
liquefied  gelatine  is  quite  transparent,  and  there  is  a  slight  flocculent 
deposit  at  the  bottom  of  the  tube. 


216  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

Ou  surface  of  agar  stick-culture  at  eud  of  two  weeks  a  tUiu,  pale- 
brown  layer. 

Colonies  in  gelatine  roll-tubes  at  end  of  24  hours,  at  22°  C,  spherical, 
with  a  milky  oi>acity,  and  having  a  transparent  marginal  zone,  as  seen 
in  Fig.  7,  PI.  xiv. 

Under  the  microscope  the  colonies  are  seen  to  be  finely  granular.  At 
the  eud  of  24  hours  liquefaction  commences. 

No  growth  on  potato. 

Not  pathogenic  for  rabbits. 

For  morphology,  see  Fig.  1,  PI.  xiv. 

BACILLI   OBTAINED   IN   COMPARATIVE   EXPERIMENTS. 

No.  29.  Bacillus  A,  Havana,  1889. 

Obtained  from  contents  of  sewer  at  its  exit,  near  the  margin  of  the 
bay. 

A  motile,  liquefying,  aerobic  bacillus ;  forms  large  oval  spores. 

Liquefies  gelatine  slowly ;  a  rather  thick  mycoderma  forms  ou  surface 
of  liquefied  gelatine. 

Milk-white  growth  on  surface  of  nutrient  agar. 

In  agar  roll-tubes  a  thin  spreading  growth  with  irregular  margins. 

Semi-fluid  growth  upon  potato,  with  shining  surface,  as  if  varnished ; 
growth  very  rapid;  at  end  of  24 hours,  at  27°  C,  covers  entire  surface; 
later  a  membranous  film  wrinkled  and  raised  in  ridges  at  center. 

For  morphology,  see  Fig.  3,  PI.  xiv. 

No.  30.  Bacillus  E,  Havana,  1889. 

Obtained  from  feces  of  healthy  individual. 
A  motionless,  liquefying  bacillus. 
Forms  large  oval  spores. 

Dry  and  rather  thick  white  mass  upon  surface  of  agar  stick -culture. 
Eapid  growth  on  potato,  forming  a  white,  viscid,  spongy,  or  yeast- 
like mass.    For  morphology,  see  Fig.  2,  PI.  xiv. 

No.  31.  Bacillus  U,  Havana,  1889. 
Accidental  colony  from  the  air. 
Dirty-white  growth  on  potato. 
Not  studied  further.     See  Fig.  5,  PI.  xrv. 

No.  32.  Bacillus  Y,  Havana,  1889. 

Accidental  colony  from  the  air.  A  large  torula-like  bacillus.  Lique- 
fies gelatine;  the  liquefied  gelatine  is  very  viscid.     (See  Fig.  6,  PI. 

XIV.) 

No.  33.  Bacillus  gracilis  (Sternberg).     (Bacillus  17,  1890.) 

Obtained  from  liver  kept  48  hours  in  antiseptic  wrapping,  compara- 
tive autopsy  No.  11. 

A  non-motile,  non-liquefying  bacillus  in  long  chains  composed  of  short 
oval  elements.     (See  Fig.  1,  PL  xvi.) 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  217 

In  gelatine  stick-cultnre  at  22°  C,  at  end  of  5  days  a  rather  thick 
white  mass  at  point  of  puuctnre,  covering  one-third  of  the  surface, 
closely  crowded,  opaque  colonies  at  bottom  of  line  of  ijuncture  and 
slender  branching  outgrowth  above. 

In  gelatine  roll  tubes  the  deep  colonies  are  opaque  and  spherical  j 
superficial  colonies  circular,  or  slightly  irregular  in  outline,  white  in 
color,  and  opaque  or  slightly  translusceut.     (See  Figs.  3  and  5,  PI. 

XVI.) 

In  nutrient  agar,  at  end  of  5  days,  at  22°  C,  milk-white  growth  on 
surface;  opaque  growth  to  bottom  of  line  of  puncture. 

On  potato,  at  end  of  5  days,  at  22°  0.,  rather  thick  cream- white  growth 
with  irregular  margins  along  line  of  impfstrich. 

Cultures  in  bonillon  have  a  milky  opacity  and  a  very  disagreeable 
odor. 

Grows  in  agua  coco  without  formation  of  gas. 

No  formation  of  spores  observed. 

This  bacillus  is  ijathogenic  for  rabbits  when  injected  into  the  cavity 
of  the  abdomen,  as  is  shown  by  the  following  experiments : 

Baltimore,  March  14,  1890,  9:30  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit 
No.  268,  one-half  cubic  centimetre  bouillon  culture  of  bacillus  17.  Animal  found 
dead  next  morning.  Liver  and  spleen  normal,  kidneys  intensely  hpersemic.  No 
bacilli  seen  in  smear  preparation  from  liver  and  kidneys.  Bacillus  17  recovered  in 
culture  from  blood  of  heart. 

Baltimore,  March.  15,  9  a.  m. — Injected  into  cavity  of  abdomen  of  rabbit  No.  272, 
weight  580  grammes,  1  cubic  centimetre  bouillon  culture  bacillus  17.  Very  sick  at 
12:30,  died  at  3:30.  A  few  bacilli  in  chains  in  preparation  from  blood  of  heart.  Ba- 
cillus 17  recovered  in  cultures  from  blood  of  heart. 

Baltimore,  March  15,  9  a.  m, — Injected  into  cavity  of  abdomen  of  rabbit  No.  273, 
vreight  1,430  grammes,  1  cubic  centimetre  bouillon  culture  of  bacillus  17.  Animal  died 
at  12:30  same  day. 

Baltimore,  March  31. — Injected  into  cavity  of  abdomen  of  rabbit  No.  283,  weight 
1,220  grammes,  1  cubic  centimetre  bouillon  culture  bacillus  17.     Result  negative. 

Baltimore,  April  4. — Injected  into  cavity  of  abdomen  of  rabbit  284,  weight  1,560 
grammes,  1  cubic  centimetre  bouillon  culture  bacillus  17.     Result  negative. 

SUBCUTAKEOUS   INJECTIONS  t)0   NOT  KILL   RABBITS. 

Baltimore,  March  17. — Injected  subcutaneously  into  rabbit  No.  276,  weight  276 
grammes,  1  cubic  centimetre  bouillon  culture  of  bacillus  17,     Result  negative. 

Baltimore,  March  31. — Injected  subcutaneously  into  rabbit  No.  285,  weight  910 
grammes,  1^  cubic  centimetres  bouillon  culture  of  bacillus  17.     Result  negative. 

Baltimore,  March  31. — Injected  subcutaneously  into  rabbit  No.  286,  weight  1,280 
grammes,  2  cubic  centimetres  culture  in  bouillon.     Result  negative. 

STERILIZED   CULTURES   NOT  PATHOGENIC  FOR  RABBITS. 

Baltimore,  April  1. — Injected  into  cavity  of  abdomen  of  rabbit  No.  287,  weight  1,400 
grammes,  8  cubic  centimetres  sterilized  culture  (at  160°  F.)  of  bacillus  1  7.  Result 
negative. 

Baltimore,  March  18. — Injected  into  cavity  of  abdomen  of  rabbit  No.  280,  weight 
940  grammes,  5  cubic  centimetres  sterilized  culture  (at  160°  F.)  of  bacillus  17.  Re- 
sult negative. 


218  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 

NOT  PATHOGENIC  FOR   GUINEA-PIGS, 

Baltimore,  December  5. — Injected  subcutaneously  into  guinea-pig  No.  184,  1  cubic 
centimetre  culture  of  bacillus  17  in  agua  coco.     Result  negative. 

Baltimore,  March  17.— Injected  subcutaneously  into  guinea-pig  210,  3  minims  bouil- 
lon culture  bacillus  17.  Result  negative.  Marcb  22,  injected  into  cavity  of  tbe  ab- 
domen of  same  animal  H  cubic  centimetres  bouillon  culture  bacillus  17.  Result  neg- 
ative. 

Baltimore,  March  17. — Injected  into  cavity  of  abdomen  of  gaiuea-pig  211,  1  cubic 
centimetre  bouillon  culture  bacillus  17.     Result  negative. 

No.  34.  Bacillus  coll  similia  (Sternberg).    (Bacillus  24,  1890.) 

Obtained  from  liver  kept  in  antiseptic  wrapping,  comparative  autopsy 
No.  11. 

A  non-motile,  non-liquefying  bacillus,  resembling  the  Bacterium  coli 
commune  of  Escberich,  but  differing  from  it  in  tbe  characters  of  its 
colonies  in  gelatine  roll-tubes,  in  its  growth  on  potato,  etc.  (See  Figs. 
4  and  7,  PI.  xvi.) 

Growth  in  flesh  peptone  gelatine  as  shown  in  Fig.  6,  PI.  xvi. 

In  gelatine  roll-tubes  the  superficial  colonies  are  homogeneous  and 
translucent  at  the  end  of  two  days;  the  deep  colonies  spherical  and 
pale  brown  in  color.  Later  the  deep  colonies  become  opaque,  and  the 
superficial  colonies  are  quite  thin  and  have  a  pale  brown  color. 

On  potato  there  is  at  22°  0.  a  thick  dirty-white  or  light-brown  growth 
along  the  impfstrich. 

Not  pathogenic  for  rabbits  or  guinea-pigs  (single  experiment  on  each 
animal). 
No.  35.  Bacillus  B,  Havana,  1889. 

Obtained  in  auaerobic  culture  from  liver  of  case  of  heart  disease,  kept 
48  hours  in  antiseptic  wrapping.     Grows  at  bottom  of  long  agar  stick. 
No  growth  in  gelatine  stick- culture.     (See  Fig.  1,  PI.  xv.) 

MICROCOCCI. 

No.  1.  Staphylococcus  pyogenes  aureus. 

Obtained  in  cultures  from  yellow-fever  liver  kept  for  48  hours  in  an 
antiseptic  wrapping  (case  8,  Havana,  1888) ;  also  from  stomach  (case  11, 
Decatur,  1888). 
No.  2.  Streptococcus  cadaveris  (Sternberg).     (Streptococcus  pyogenes  ?) 

Obtained  from  liver  of  case  14  (Hav.,  1889). 

Afacultative  anaerobic;  does  not  liquefy|gelatine;  forms  long  chains  of 
spherical  or  slightly  oval  elements.  The  cocci  when  in  process  of  division 
resemble  a  short  bacillus  with  stained  ends,  and  a  chain  of  such  divid- 
ing cocci  may  be  mistaken  for  a  chain  of  oval  bacilli.  Indeed,  I  at  first 
considered  this  a  bacillus  resembling  that  of  Babes,  and  designated  it 
bacillus  0  in  the  list  of  microorganisms  isolated  by  me  in  1889. 

No  growth  on  surface  of  gelatine  stick-cultures ;  opaque  colonies 
along  the  line  of  puncture  larger  and  more  opaque  than  in  similar  cul- 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    PEVER.  219 

tures  of  streptococcus  pyogenes  made  at  the  same  time.  Later  the  iso- 
lated colonies  at  bottom  of  line  of  puncture  are  irregular  in  outline  and 
granular. 

Thin  translucent  growth  on  surface  of  agar  culture  in  Baltimore.  In 
Havana  the  growth  was  more  abundant,  forming  a  white  mass  about 
the  point  of  puncture.  Grows  well  in  an  acid  medium  (1:500  of  hydro- 
chloric acid).  In  bouillon  and  agua  coco  it  forms  little  ilocculi  made 
up  of  chains. 

In  old  agar  cultures  is  very  small  and  not  iu  chains.  Culture  in  veal 
broth  gives  long  chains  and  the  cocci  are  much  larger.  The  individual 
elements  may  vary  greatly  in  size  in  the  same  chain. 

Very  thin  white  growth  on  surface  of  potato  at  end  of  12  days.  Not 
found  to  be  pathogenic  for  guinea-pigs  or  rabbits.  For  morphology  see 
photomicrograph,  Fig.  1,  PI.  xvii. 

No.  3.  streptococcus  Havaniensis  (Sternberg). 

Obtained  in  acid  and  transparent  liquid  vomited  by  yellow-f'iver 
patient  iu  Military  Hospital,  Havana,  1889,  after  having  been  kept  for 
24  hours  in  collecting  bulb.     (See  Fig.  2,  PL  xvii.) 

No.  4.  Streptococcus   liquefaciens  (Sternberg).     (Streptococcus  coli  gracilis  of 
Escbericli  ?) 

Obtained  from  liver  case  42,  48  hours  in  laboratory ;  also  from  liver 
case  31,  and  intestine  case  15 ;  also  in  comparative  autopsies  in  Balti- 
more. 

A  liquefying  coccus  which  forms  short  chains,  possibly  the  Babes 
microbe. 

In  gelatine  stick  cultures  the  gelatine  is  entirely  liquefied  at  the  end 
of  a  week  as  seen  in  Fig.  7,  PI.  xvii.  The  liquefied  gelatine  is  but  slightly 
opalescent  and  there  is  a  scanty  deposit  at  the  bottom  of  the  tube. 

In  nutrient  agar  there  is  a  scanty  growth  at  the  point  of  puncture 
and  closely  crowded  opaque  colonies  to  bottom  of  tbe  line  of  puncture. 

Thin  and  limited  dry  white  growth  on  i)otato  at  end  of  5  days. 

Not  pathogenic  for  guinea  pigs  or  rabbits. 

For  morphology  see  photomicrograph.  Fig.  4,  PI.  xvii. 

No.  5.  Micrococcus  hepaticus  (Sternberg). 

Obtained  iu  culture  from  liver,  case  8.  kept  48  hours  in  antiseptic 
wrapping.    A  diijlococcus.     (See  Fig.  2,  PI.  xviii.) 

Does  not  liquefy  gelatine. 

In  gelatine  roll  tubes  the  superficial  colonies  are  spherical  and  trans- 
lucent ;  deep  colonies  at  first  translucent  and  homogeneous,  become  in  3 
or  4  days  more  or  less  lobate,  and  pale  brown  in  color  by  transmitted 
light. 

Not  pathogenic  for  rabbits. 

No.  6.  Micrococcus  Finlayensis  (Sternberg). 

Obtained  by  Dr.  Finlay  in  cultures  from  the  liver  and  spleen  of  a  yel- 
low-fever case  and  sent  to  me  by  him  in  August,  1888. 


220  ETIOLOGY    AND   PREVENTION    OF    YELLOW    FEVER. 

This  is  a  liqaefyiDg  stapliylococcus,  which,  like  other  staphylococci,  is 
sometimes  fouucl  iu  groups  of  four.  Wheu  seut  to  lue  Dr.  Finlay  sup- 
posed it  to  be  identical  with  the  large  micrococcus  in  tetrads  which  he 
had  previously  encountered  in  connection  with  yellow-fever  cases,  ray 
Micrococcus  tetrageniis  versatiUis.  He  is  now  satisfied  that  it  is  a  dif- 
ferent species. 

This  coccus  differs  from  that  of  Dr.  Freire  of  Brazil  in  having  a  pale 
yellow  color  ^vhen  viewed  in  mass  upon  the  surface  of  an  agar  culture; 
while  that  of  Freire  has  a  milk-white  color.     (See  Fig.  2,  PI.  xx.) 

It  liquefies  gelatine  slowly,  forming  a  cup  shaped  cavity,  which  has  a 
very  viscid,  opaque,  pale  yellow  lining,  made  up  of  the  cocci. 

J!Jot  pathogenic  for  guinea-pigs  or  rabbits. 

For  the  morphology  of  this  coccus  see  Fig.  4,  PI.  xviii. 

No.  7.  Micrococcus  versatilis  albus. 

Accidental  colony  from  the  air,  Havana,  1889. 

A  liquefying  coccus;  often  in  groups  of  four;  very  irregular  in 
groaping  and  dimensions.  Milk-white  growth  on  surface  of  nutrient 
agar,  opaque  irregular  growth  along  line  of  puncture.  Milk-white  and 
later  grayish-white  rather  thick  growth  on  potato.  Does  not  form  gas 
or  produce  acid  reaction  in  agua  coco.     (See  Fig.  5,  PI.  xviii.) 

No.  8.  Micrococcus  kiteus. 

Obtained  in  cultures  made  from  the  surface  of  the  body  of  patients 
in  Civil  Hospital,  Havana,  1889.  Does  not  liquefy  gelatine.  Minute, 
opaque  colonies  along  line  of  puncture  in  gelatine  stick  cultures.  Tel- 
low  gTOwth  upon  surface  of  agar. 

Gamboge-yellow  growth  of  limited  extent  on  potato.  (See  Fig.  3, 
PI.  xvn.) 

Torula  gastricus  (Sternberg). 

In  my  direct  examination  of  vomited  matters  and  of  the  contents  of 
the  stomach  after  death  I  have  very  frequently  encountered  cells  of  a 
torula,  and  in  several  cases  I  have  isolated  this  in  pure  cultures.  It 
forms  a  white  mass  upon  the  surface  of  nutrient  agar  or  gelatine  cul- 
tures ;  it  does  not  liquefy  gelatine,  and  in  Esmarch  roll  tubes  it  forms 
beautiful  stellate  colonies.  The  morphology  is  shown  by  my  photo- 
micrograph. Fig.  1,  PI.  XVIII. 

The  list  of  microrganisms  above  described  by  no  means  includes 
all  of  those  encountered  in  my  studies.  I  have  notes  relating  to  many 
others,  but  not  having  found  time  to  study  their  characters  fully,  so  as 
to  differentiate  them  in  a  satisfactory  manner,  I  have  not  thought  it 
worth  while  to  make  any  further  mention  of  them. 


IX -CONCLUSIONS. 

The  experimental  data  recorded  in  this  reporc  show  that — 

The  specific  infectious  agent  in  yellow  fever  has  not  been  demonstrated. 

The  most  approved  bacteriological  methods  fail  to  demonstrate  the 
constant  presence  of  any  particular  microorganism  in  the  blood  and 
tissues  of  yellow-fever  cadavers. 

The  microorganisms  which  are  sometimes  obtained  in  cultures  from 
the  blood  and  tissues  are  present  in  comparatively  small  numbers, 
and  the  one  most  frequently  found  {Bacterium  coli  commune)  is  present 
in  the  intestine  of  healthy  individuals,  and  consequently  its  occasional 
presence  can  not  have  any  etiological  imxDort. 

A  few  scattered  bacilli  are  present  in  the  liver,  and  probably  in  other 
organs,  at  the  moment  of  death.  This  is  shown  by  preserving  portions 
of  liver,  obtained  at  a  recent  autopsy,  in  an  antiseptic  wrapping. 

At  the  end  of  24  to  48  hours  the  interior  of  a  piece  of  liver  so  pre- 
served contains  a  large  number  of  bacilli  of  various  species,  the  most 
abundant  being  those  heretofore  mentioned  as  occasionally  found  in 
fresh  liver  tissue,  viz.  Bacterium  coli  commune  and  Bacillus  cadaveris. 

Blood,  urine,  and  crushed  liver  tissue  obtained  from  a  recent  autopsy 
are  not  pathogenic,  in  moderate  amounts,  for  rabbits  or  guinea-pigs. 

Liver  tissue  preserved  in  an  antiseptic  wrapping  at  a  temperature  of 
28  to  30°  C.  for  48  hours  is  very  pathogenic  for  guinea-pigs  when 
injected  siibcutaneously. 

This  pathogenic  power  appears  to  be  due  to  the  microorganisms  pres- 
ent and  to  the  toxic  products  developed  as  a  result  of  their  growth.  It 
is  not  peculiar  to  yellow  fever,  inasmuch  as  material  preserved  in  the 
same  way  at  comparative  autopsies,  in  which  death  resulted  from  ac- 
cident or  other  diseases,  has  given  a  similar  result. 

Having  failed  to  demonstrate  the  j)resence  of  a  specific  "germ"  in 
the  blood  and  tissues  it  seems  x)robable  that  it  is  to  be  found  in  the 
alimentary  canal,  as  is  the  case  in  cholera.  But  the  extended  researches 
made  and  recorded  in  the  present  report  show  that  the  contents  of  the 
intestine  of  yellow-fever  cases  contain  a  great  variety  of  bacilli  and  not 
a  nearly  pure  culture  of  a  single  species,  as  is  the  case  in  recent  and 
typical  cases  of  cholera. 

Comparatively  few  liquefying  bacilli  are  found  in  the  feces  discharged 
during  life  or  in  the  intestinal  contents  collected  soon  after  death  from 
yellow-fever  cadavers. 

221 


222     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER, 

Ou  the  other  hand  uonliquefying  bacilli  are  very  abundant. 

The  one  most  constantly  and  abundantly  present  is  the  Bacterium  coli 
commune  of  Escherich. 

This  is  associated  with  various  other  baccilli,  some  of  which  are  strict 
anaerobics  and  some  facultative  anaerobics. 

Among  the  facultative  anaerobics  is  one — my  bacillus  x — which  has 
been  isolated  by  the  culture  method  in  a  considerable  number  of  cases 
and  may  have  been  ijresent  in  all.  This  bacillus  has  not  been  en- 
countered in  the  comparative  experiments  made.  It  is  very  pathogenic 
for  rabbits  when  injected  into  the  cavity  of  the  abdomen. 

It  is  possible  that  this  bacillus  is  concerned  in  the  etiology  of  yellow 
fever,  but  no  satisfactory  evidence  that  this  is  the  case  has  been  ob- 
tained by  experiments  on  the  lower  animals,  and  it  has  not  been  found 
in  such  numbers  as  to  warrant  the  inference  that  it  is  the  veritable 
infectious  agent. 

All  other  microorganisms  obtained  in  pure  cultures  from  yellow- 
fever  cadavers  appear  to  be  excluded,  either  by  having  been  identi- 
fied with  known  species,  or  by  having  been  found  in  comparative 
researches  made  outside  of  the  area  of  yellow-fever  prevalence,  or 
by  the  fact  that  they  have  been  found  only  in  small  numbers  and  in  a 
limited  number  of  cases. 

Finally  we  remark  that  many  facts  relating  to  the  origin  and  exten- 
sion of  yellow-fever  epidemics  give  support  to  the  inference  that  the 
specific  infectious  agent  is  present  in  the  dejecta  of  those  suffering  from 
the  disease,  and  that  accumulations  of  feoal  matter  and  of  other 
organic  material  of  animal  origin  furnish  a  suitable  nidus  for  the 
development  of  the  "germ"  when  climatic  conditions  are  favorable  for 
its  growth. 

It  may  be  that  such  a  nidus  is  essential  and  that  the  culture  media 
usually  employed  by  bacteriologists  do  not  afford  a  suitable  soil  for 
this  particular  microbe. 

It  is  also  possible  that  its  development  depends  upon  the  presence 
of  other  microorganisms  found  in  fecal  matter,  which  give  rise  to  chem- 
ical products  required  for  the  development  of  this  one. 

Some  of  the  microorganisms  present  in  the  dejecta  of  yellow-fever 
patients,  as  shown  by  stained  smear- preparations,  have  not  developed 
in  the  cultures  made,  either  aerobic,  or  anaerobic.  One  extremely 
slender,  filiform  bacillus,  which  can  only  be  seen  with  high  powers  and 
which  is  quite  abundant  in  some  of  my  preparations,  has  never  been 
obtained  in  the  cultures  made,  and  no  doubt  there  are  others  in  the 
same  category. 

That  the  yellow-fever  germ  is  a  strict  anaerobic  or  that  it  will  only 
grow  in  a  special  nidus  may  be  inferred  from  certain  facts  relating  to 
the  extension  of  epidemics. 

There  is  no  evidence  that  yellow  fever  is  propagated  by  contamina- 
tion of  the  supply  of  drinking  water,  as  frequently,  and  probably  usu- 


ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER.  223 

ally,  occurs  in  the  case  of  typhoid  fever  and  cholera.  Moreover  epi- 
demics extend  in  a  more  deliberate  manner  and  are  restricted  within  a 
more  definite  area  than  is  the  case  with  cholera  and  typhoid  fever.  It 
is  usually  at  least  ten  days  or  two  weeks  after  the  arrival  of  an  in- 
fected vessel  or  of  a  person  sick  with  the  disease  before  cases  of  local 
origin  occur;  and  these  cases  occur  in  the  immediate  vicinity  of  the 
imported  case  or  infected  vessel.  When  the  disease  has  eifected  a 
lodgment  the  area  of  infection  extends  slowly  and  usually  has  well- 
defined  boundaries.  In  towns  and  cities  having  a  common  water  sup- 
ply one  portion  remains  perfectly  healthy,  while  another,  and  usually 
the  most  filthj"  portion,  may  be  decimated  by  the  scourge. 

The  experimental  evidence  recorded  and  the  facts  just  stated  seem  to  jus- 
tify the  recommendation  that  the  dejecta  of  yellow-fever  patients  should  he 
regarded  as  infectious  material  and  that  such  material  should  never  be 
thrown  into  privy  vaults  or  upon  the  soil  until  it  has  been  completely 
disinfected. 

This  rule  thoroughly  enforced,  together  -with  an  efQcient  quarantine 
service  and  proper  attention  to  the  sanitary  police  of  our  exposed  sea- 
port cities,  would,  I  believe,  effectually  prevent  this  pestilential  disease 
from  again  obtaining  a  foothold  within  the  limits  of  the  United  States. 


224  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVEK. 


PLATE  L 

Yellow  fever  blood ;  first  day  of  sickness ;  fatal  case.  Photomicrograph  made  in 
Havana  in  1879.  X  1,500  diameters;  enlarged  from  a  photomicrograph  of  500  diame- 
ters made  with  Beck's  one-fifth  inch  objective,  dry. 

[Extracts  from  report  of  Havana  Commission,  1879.  J 

"  In  Havana  Dr.  Sternberg  gave  a  large  share  of  his  time  to  the  microscopic  examina- 
tion and  photography  of  the  blood.  No  chemical  examination  was  attempted.  The 
patients  from  whom  specimens  of  blood  were  obtained  were  mostly  soldiers  in  the 
military  hospital  of  San  Ambrosio.  Ninety-eight  specimens  from  41  undoubted  cases 
of  yellow  fever  were  carefully  studied  and  105  photographic  negatives  were  made, 
which  show  satisfactorily  everything  demonstrable  by  the  microscope. 

These  photographs  were  mostly  made  with  a  magnifying  power  of  1,450  diameters, 
obtained  by  the  use  of  Zeiss's  one-eighteenth  inch  objective,  and  Tolles's  amplifier. 
Probably  no  better  lens  than  the  Zeiss  one-eighteenth  (oil  immersion)  could  have 
been  obtained  for  this  work,  and  it  is  doubtful  whether  any  objective  has  ever  been 
made  capable  of  showing  more  than  is  revealed  by  this  magnificent  lens.  With  the 
power  used,  organisms  much  smaller  than  those  described  as  existing  in  the  blood  of 
charbon  or  of  relapsing  fever  would  be  clearly  defined. 

If  there  is  any  organism  in  the  blood  of  yellow  fever  demonstrable  by  the  highest 
powers  of  the  microscope  as  at  i)resent  perfected,  the  photomicrographs  taken  in 
Havana  should  show  it.  No  such  organism  is  shown  in  any  preparation  photographed 
immediately  after  collection.  But  in  certain  specimens,  kept  under  observation  In 
culture  cells,  hyphomycetoua  fungi  and  spherical  bacteria  made  their  appearance 
after  an  interval  of  from  1  to  7  days.  Theappearanceof  these  organisms  was,  however, 
exceptional,  and,  in  several  specimens  taken  from  the  same  individual  at  the  same 
time,  it  occurred  that  in  one  or  two  a  certain  fungus  made  its  appearance  and  in 
others  it  did  not.  This  fact  shows  that  the  method  employed  can  not  be  depended 
upon  for  the  exclusion  of  atmospheric  germs,  but  does  not  affect  the  value  of  the  re- 
sult in  the  considerable  number  of  instances  in  which  no  development  of  organisms 
occurred  in  culture  cells  in  which  blood  in  a  moist  state  was  kept  under  daily  obser- 
vation for  a  week  or  more. 

The  method  employed  seemed  the  only  one  practicable  for  obtaining  blood  from  a 
large  number  of  individuals  without  inflicting  unwarrantable  pain  and  disturbance 
upon  the  sick.  It  was  as  follows  :  One  of  the  patient's  fingers  was  carefully  washed 
with  a  wet  towel  (wet  sometimes  with  alcohol  and  at  others  with  water)  and  a 
puncture  was  made  just  back  of  the  matrix  of  the  nail  with  a  small,  triangular- 
pointed  trocar.  As  quickly  as  possible  a  number  of  thin  glass  covers  were  applied 
to  the  drop  of  blood  which  flowed,  and  these  were  then  inverted  over  shallow  cells 
in  clean  glass  slips,  being  attached  usually  by  a  circle  of  white  zinc  cement.  In  dry 
preparations,  which  are  most  suitable  for  photography,  the  small  drop  of  blood  was 
spread  upon  the  thin  glass  cover  by  means  of  the  end  of  a  glass  slip. 

The  thin  glass  covers  were  taken  from  a  bottle  of  alcohol  and  cleaned  immediately 
before  using,  and  usually  the  glass  slips  were  heated  shortly  before  applying  the 
covers,  for  the  purpose  of  destroying  any  atmospheric  germs  which  might  have 
lodged  upon  them.  These  precautions  were  not,  however,  sufficient  to  prevent  the 
inoculation  of  certain  specimens  by  germs  floating  in  the  atmosphere  (Penicillium 
spores  and  micrococci) ;  and  in  nearly  every  specimen  the  presence  of  epithelial  cells, 
and  occasionally  of  a  fiber  of  cotton  or  linen,  gave  evidence  that  under  the  circum- 
stances such  contamination  was  unavoidable.  It  is  therefore  believed  that  any 
organism  developing  in  the  blood  of  yellow  fever,  or  of  other  diseases,  collected 
by  the  method  described  or  by  any  similar  method,  can  have  no  great  significauce 
unless  it  is  found  to  develop  as  a  rule  (not  occasionally)  in  the  blood  of  patients  suf- 
fering from  the  disease  in  question,  and  is  proved  by  comparative  tests  not  to  develop 
in  the  blood  of  healthy  individuals  obtained  at  the  same  time  and  by  the  same 
method. 

Tried  by  this  test  it  must  be  admitted  that  certain  fungi  and  groups  of  micrococci, 
shown  in  photographs  taken  from  specimens  of  yellow  fever  blood  collected  at  the 
military  hospital  aud  preserved  in  culture  cells,  can  not  reasonably  be  supposed  to  be 
peculiar  to  or  to  have  any  casual  relation  to  this  disease." 


PLATE    I. 


226     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 


PLATE  II. 

Fia.  1.  Yellow  fever  blood ;  fifth  day;  fatal  case.  Photomlcrograpli  made  in  Havana 
in  1879.  X  1,450  diameters  by  Zeiss's  one-eigbteenth  bom.  oil  immersion 
objective  and  Tolles's  amplifier. 

Fig.  2.  YeUow  fever  blood ;  first  day;  fatal  case.  Pbotomicrograpb  made  in  Havana 
in  1879 ;  same  amplification  as  Fig  1. 

Fig.  3.  Yellow  fever  blood ;  fiftb  day ;  fatal  case.  Havana,  1879.  Same  amplifica- 
tion as  Fig.  1. 

Fig.  4.  Leucocyte  in  yellow  fever  blood  kept  in  a  culture  cell  for  two  days  ;  eighth 
day  of  sickness.     Fatal  case.     Havana,  1879.     X  650  diameters. 

Fig.  5.  Leucocyte  in  yellow  fever  blood  of  eighth  day  ;  fatal  case  (same  as  Fig.  3). 
Kept  in  culture  cell  for  two  days.     X  650  diameters. 

lExtract  from  preliminary  report  of  Havana  Yellow  Fever  Commission  to  Kational  Board  of  Health, 

submitted  November  18,  1879.] 

"  The  most  important  observation  made  relates  to  certain  granules  in  the  white 
corpuscles  shown  in  many  of  the  photomicrographs  taken.  From  the  manner  in 
which  these  granules  refract  light,  and  for  other  reasons,  they  are  believed  by  Dr. 
Sternberg  to  be  fat,  and  to  represent  a  fatty  degeneration  of  the  leucocytes.  The 
blood  of  twelve  healthy  individuals  was  examined  in  Havana,  for  comparison,  and  in 
nearly  every  case  an  occasional  leucocyte  was  found  to  contain  a  few  (one  or  two) 
granules  indistinguishable  from  those  found  in  the  blood  of  yellow  fever  ;  but  this 
was  the  rare  exception,  while  in  severe  cases  of  yellow  fever  the  granules  were 
abundant,  and  nearly  every  white  corpuscle  contained  some  of  them." 

Remark. — In  similar  preparations  (dry)  of  blood  from  the  finger  of  yellow  fever 
patients,  made  in  Rio  de  Janeiro  in  1887,  the  same  refractive  granules  in  the  leuco- 
cytes were  encountered.  That  they  are  not  peculiar  to  yellow  fever  is  shown  by  the 
fact  that  similar  granules  were  present  in  the  leucocytes,  in  dry  mounts,  of  blood 
from  the  finger  of  persons  suffering  from  beri-beri  in  one  of  the  hospitals  of  Eio 
de  Janeiro. 


PLATE    11. 


Fig.  4. 


Fig.  I. 


Fig.  3. 


Fig.  2. 


HEIIOTVPE  PRINTING  CO.    BOSTON, 


228     ETIOLOGi  AND  PEEVENTION  OF  YELLOW  FEVEE. 


PLATE  m. 

Fig.  1.  Micrococcus  of  Freire,  from  the  culture  given  by  him  to  Dr.  Sternberg  at  the 
time  of  Ms  visit  to  Brazil.    Fuchsin  stain  ;  x  1,000. 

Fig.  2.  Micrococcus  of  Freire,  from  an  agar  culture ;  fuchsin  stain  ;  X  1,000. 

Fig.  3.  Micrococcus  tetragenus  versatilis  (Sternberg),  (tetragenua  febris  flavse  of  Fin- 
lay).  From  a  single  colony  in  a  gelatine  Esmarch  roll-tube.  Fuchsin 
stain ;  X  1,000. 

Fig.  4.  Bacillus  of  Carmona,  cultivated  from  yellow  fever  urine,  from  a  slide  mounted 
in  Dr.  Carmona's  laboratory  by  Dr.  Gavina,  and  presented  by  him  to  Dr. 
Sternberg  at  the  time  of  his  visit  to  Mexico.     Fuchsin  stain;   X  1,000. 

Fig.  5.  Culture  of  Freire's  micrococcus  in  flesh-peptone-gelatine  at  the  end  of  8  days 
at  22°  C. 

Fig.  6.  Culture  of  Freire's  micrococcus  in  flesh-peptone-gelatine  at  end  of  4  days  at 
22°  C. 

Fig.  7.  Micrococcus  tetragenus  versatilis.  Culture  in  flesh -pep  tone-gelatine  at  end  of 
2  weeks  at  22°  C. 


PLATE    III, 


Fig.   I. 


Fig.  3. 


Fig.   2, 


Fig. 


Fig.  5, 


Fig.  6. 


Fig.  7. 


eLIOTYPE  printing   CO.    BOSTON. 


230     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 


PLATE  rV. 

Fig.  1.  Sadllus  l^ina  Uthalis  (Steruberg) — bacillus  of  Gibier.     From  surface  of  agar 

culture,  12  days  old.     Fuchsin  stain ;   X  1000. 
Fig.  2.  Bacillus  lepina  lethalis  (Sternberg).     From   bouillon   culture,  24   hours   old. 

Fuchsin  stain  ;   X 1000. 
Fig.  3.  Colonies  of  Gibier's  bacillus  in  gelatine  roll-tube ;  end  of  48  hours  at  room 

temperature  (about  20°  C);  X  5  diameters. 
Fig.  4.  Single  colony  of  Gibier's  bacillus  in  gelatine  roll-tube  at  end  of  3  days  at 

room  teuiporature ;   liquefaction  of  gelatine  around  the  colony ;    X  5 

diameters. 
Fig.  5.  Culture  of  Gibier's  bacillus  in  flesh-peptoue-gelatine ;  end  of  4  days  at  22°  C. 
Fig.  6.  Culture  of  Gibier's  bacillus  in  flesh -peptone-gelatine;  end  of  5  days  at  22°  C. 
Fig.  7.  Culture  of  Gibier's  bacillus  in  flesh-peptone-gelatine;  end  of  8  days  at  22°  C. 


PLATE    IV. 


Fig.   I. 


Fig.  3. 


Fig.  2. 


Fig.  4. 


y 


Fig.  5. 


Fig.  6. 


P'ig.  7. 


HELIOTYPE    PRINTING   CO.    SOSfON. 


232     ETIOLOGY  AND  PKEVENTION  OF  YELLOW  FEVEE. 


PLATE  V. 

Fig.  1.  Bacillus  a;  "stick-culture"  in  flesh-peptone-gelatine  (20  percent,  of  gela- 
tine) ;  from  a  photograph. 

Fig.  2.  Portion  of  same  stick-culture  shown  in  Fig.  1,  magnified  about  4  diameters  ; 
from  a  photograph. 

Fig.  3.  BaciUusa;  a  gelatine  stick-culture  obtained  from  the  feathery  outgrowths 
shown  in  Figs.  1  and  2  (20  per  cent,  of  gelatine). 

YiG.  4.  Emerich's  bacillus  cultivated  in  20  per  cent,  gelatine,  at  27°  C.  (80.6°  F.) 

Fig.  5.  Bacterium  coli  commune  of  Escherich,  cultivated  in  20  per  cent,  gelatine  at 
27°  C.  (80-6°  F.) 

Fig.  6.  Bacillus  a ;  magnified  1250  diameters.  From  a  photo-micrograph  by  Dr.  Stern- 
berg. 

Fig.  7.  Colonies  of  bacillus  a  in  flesh-peptone-gelatine ;  a  superficial  colonies  in 
rosettes ;  h  deep  colonies,  usual  form ;  c  superficial  colonies,  usual  form. 


T'l.ATE  V" 


-_:^s0 . 


f.         ■"' 


i\    \ 


J"ici  4 


Firt  3 


Pirt   5 


A.HoEn  SCa.LrthncaustJcBaHimnrE. 


234  ETIOLOGY   AND   PREVENTION   OF   YELLOW    FEVER. 


PLATE  VI. 

Fig.  1.  Bacillus  x  (Havana,  1889.)  Smear  preparation  from  snrfaee  of  liver  of  rab- 
bit 274,  which  died  at  end  of  24  hours  after  receiving  in  cavity  of  abdo- 
domen  3 .  cubic  centimeters  of  a  bouillon  culture  of  bacillus  x.  The 
bacilli  are  smaller  than  in  recent  cultures,  but  a  pure  culture  was  ob- 
tained from  the  peritoneal  cavity  of  this  rabbit  in  which  the  bacilli  had 
the  usual  size  as  seen  in  Fig.  3.      Fuchsin  stain  ;   X  1000. 

Fig.  2.  Bacillus  x,  from  a  potato  culture.  The  potato  had  an  acid  reaction  and  the 
bacilli  are  unusually  large.  The  culture  was  proved  to  be  pure  by 
making  gelatine  roll-tubes  in  which  the  colonies  had  the  usual  charac- 
ters and  the  bacilli  were  of  the  usual  dimensions.  Fuchsin  stain; 
X  1000. 

Fig.  3.  Bacillus  x,  from  single  colony  in  gelatine  roll-tube.    Fuchsin  stain ;  X  1000. 

Fig.  4.  Bacillus  x,  from  potato  culture  of  4  days.    Fuchsin  stain  ;   X  1000. 

Fig.  5.  Bacillus  x,  colonies  in  gelatine  roll-tube ;  three  days  at  20°  C. ;  X  6  diame- 
t9rs. 

Fig.  6.  Bacillus  x;  colonies  in  gelatine  roll  tube ;  48  hours  at22°C. ;  X  10  diame- 
ters. 

Fig.  7.  Bacillua  «,  culture  in  flesh-peptone-gelatine  j  48  hours  at  22°  C. 


PLATE    VI. 


;l^i^ 


Fig.   I, 


.V,  »'.>.//,' 


•  '.  - 


Fig.  3, 


.^4 


ASt 


Fig.  2. 


Fig. 


Fig.  7, 


Fig.  6. 


HELIOTYPE  PRINTING  CO.    BOSTON, 


236  ETIOLOGY   AND   PREVENTION    OF   YELLOW   FEVEE. 


PLATE  VII. 

Fig.  1.  Bacillus  acidiformans  (Sternberg).     From  a  potato  culture ;  48  hours  at  22"  C. 

Fuchsiu  stain;   X  1000. 

Fig.  2.  BaciUus  acidiformans  in  a  leucocyte  (phagocyte)  from  liver  of  rabbit  inocu- 
lated with  this  bacillug.     Fnchsin  stain  ;   X  1000. 

Fig.  3.  Group  of  leucocytes  containing  B.  acidiformans,  from  blood  of  guinea-pig 
inoculated  with  a  culture  of  this  bacillus.     Fuchsiu  stain;   X  1000. 

Fig.  4.  Bacillus  a,  Havana,  1888.  {Bacterium  calx  commune.)  From  a  bouillon  cul- 
ture.    Bismark  brown  stain  ;    X  82.5. 

Fig.  o.  Colonies  of  Bacterium  coli  commune  in  gelatine  roll  tube;  end  of  48  hours, at 
22-  C.     X  10  diameters. 

Fig.  6.  Single  colony  of  BaciUus  acidiformans,  in  gelatine  roll  tube,  end  of  2  weeks. 
X  10  diameters. 

Fig.  7.  Bacillus  acidiformans,  "stick"  culture  in  glycerine-agar,  showing  the  split- 
tiug  up  of  the  agar  medium  by  the  formation  gas. 

Fig.  8.  Bacillus  acidiformans.  Culture  in  flesh-peptone-gelatine;  end  of  4  days,  at 
22°  C. 


PLATE    VII, 


ft**.     •.«•-' 


# 


Ml 


Fig.   2. 


# 


P'iG. 


Fig.   5. 


i^IG.    (D. 


238     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 


PLATE  VIII. 

Fig.  1.  Bacillus  liepaUeus  fortuitvs  (Sternberg).    From  an  agar  culture  of  24  Lours 

Fuchsin  stain ;  X  1000. 
Fig.  2.  Bacillus  intestinus  motilis  (Sternberg).     From  a  potato  culture,  10  days  old. 

Fuchsin  stain  ;  X  1000. 
Fig.  3.  Bacillus  cavia  for luUus  (Sternberg).     From  potato  culture  of  9  days.    Fucb- 

sin  stain ;  X  1000. 
Fig.  4.  Bacillus  eavicida  Havaniensis  (Sternbeig).    From  a  potato  culture  of  2  days. 

Fucbsin  stain ;.  X  1000. 
Fig.  5.  Colonies  of  i>aciW«s7iepaiicMs/oriMi(M8 in flesb-peptone-gelatine roll-tube;  end 

of  48  hours  at  22°  C.  X  10. 
Fig.  6.  Colonies  of  Bacillus  intestinus  motilis  in  gelatine  roll-tube ;  end  of  24  hours, 

at  22°  C.  X  10. 
Fig.  7.  Culture  in  flesh-peptone-gelatine  of  B.  intesiinus  motilis ;  end  of  4  days,  at 

22°  C. 
Fig.  8.  Culture  in  flesh-peptone-gelatine  of  B.  hepaticus  fortuitus  y  end  of  4  days,  at 

22°  C. 


PLATE    VIII, 


' '  ^  • 


tiv'*-?  ; 


Fig.   I 


c^ 


Fig.   2, 


Fig.  5, 


Fig.  6. 


240  ETIOLOGY   AND   PREVENTION"    OF    YELLOW    FEVER. 


PLATE  IX. 

Fig.    1.   Bacillus  Micrococcus  Havaniensis    (Sternberg).      Surface  of  agar  cnlture, 

Fuchsin  stain  ;    X  1,000. 
Fig.   2.    Bacillus  fiuorescens  liquefaciens.     From  single  colony  in  gelatine  roll-tube. 

Fuchsin  stain;   X  1,000. 
Fig.  3.  Bacillus  vacuolosis  (Sternberg).     From  potato  culture,  4  days  old.     Fuchsin 

stain;   X  1,000. 
Fig.  4.  Bacillus  vacuolosis,  from  surface  of  agar  culture,  6  days  old;  showing  in- 

Tolution  forms.     Fuchsin  stain  ;   X  1,000. 
Fig.  5.  Bacilhis  vacuolosis,  single  colony  in  gelatine  roll-tube;  end  of  5  days,  at20°C.; 

XlO. 
Fig.  6.  Bacillus  vacuolosis  culture  :n  flesh-peptone-gelatine  ;  end  of  3  days,  at  20°C. 


PLATE    IX. 


Fig.   2, 


IG. 


Fig. 


Fig.  5, 


Fig.  6. 


LIOTVPE  PRINTING  CO.,   BOSTON 


242     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVER. 


PLATE  X. 

Fig.  1.  ^adnMSjpi/oeyamMS  from  potato  culture  of  24  Hours.     Fuschsin  stain  J  x  1,000. 
Fig.  2.  Bacillus  liquefaciens  commune  (StevnheTg) .     From  gelatine  culture.     Fuchsin 

stain ;   X  825  diameters. 
Fig.  3.  Colonies  of  B.  ])iiocyanus  in  gelatine  roll-tube;  end  of  2  days,  at  20°C.;   X  15. 
Fig.  4.  Liquefying  colonies  of  B.  pyocyanus  in  gelatine  roll-tube;  end  of  3  days,  at 

20OC.;   X  15. 
Fig.  5.  B.  pyocyanus  Culture  in  flesh-peptone-gelatine  ;  end  of  24  hours,  at  22°C. 
Fig.  6.  B.  liquefaciens  commune;  culture  in  flesh-peptone-gelatine ;  end  of  24  hours, 

at  220C. 


PLATE    X. 


Fig.   I. 


":-;^  *ci:.. 


»  —         1  A        V»    '  *     > 


^V    •-!;,  \*,« 


P'lG.    2. 


Fig.  5, 


^^^j^00t''' 


Fig.  3. 


Fig.  6. 


Fig.  4. 


HELIOTVPE  PRINTING  CO.   BOSTON, 


244  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


PLATE  XL 

Fig.  1.  Bacillus  suhtilis  similis  (Sternberg).     From  potato  culture  of  5  days.    Fuchsin 

stain;   X  1000. 
Fig.  2.    Colonies  of  B.  suMilis  similis  in  gelatine  roll  tube  ;  showing  liquefaction  of 

the  gelatine  ;  end  of  48  hours,  at  room  temperature,  X  6. 
Fig.  3.  Bacillus  renalis  forttiitus    (Sternberg).      From    gelatine    culture.      Fuchsin 

stain;   X  1000. 
Fig.  4.  Bacillus  infestinus  liquefaolens  (Sternberg).     From  a  potato  culture.     Fuchsin 

stain;   X  1000. 
Fig.  5.  Bacillus  intestinus  liquefaciens.    Culture  in  flesh-peptone-gelatine ;  end  of  24 

hours,  at  22'^  C. 


PLATE    XL 


y^ 


4^ 

^0 


Fig.   I 


0 


Fig.  2. 


Fig.  3. 


Fig. 


H=l  tOTYPF    PRlf 


24:6  ETIOLOGY   AND    PREVENTION    OF    YELLOW    FEVEE. 


PLATE  XIL 

Fig.  1.  Bacillus  cadaveris  (Sternberg).    Smear  preparation  from  liver  of  yellow  fever 

case,  kept  48  hours  in  antiseptic  wrapping.     Fuchsin  stain  ;   X  1000. 
Fig.  2.  Bacillus  cadaveris   (Sternberg).     From    anaerobic  culture  in   glycerine-agar 

roll-tube:  contains  also  a  micrococcus  (see  Fig.  1,  PL  XVII).     Fuchsin 

stain  X  1000. 
Fig.  3.  Bacillus  cadaveris.    From  anaerobic  culture  in  glycerine-agar  roll-tube ;  X 

1000. 
Fig.  4.  Clostridium   cadaveris  (Sternberg).    From   surface  of  an  agar  culture ;  x 

1000. 


PLATE    XII. 


Fig.    I 


Fig.   2, 


Fig.  3. 


i      ^    /I  -7     / 


Fig.  4. 


248  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVEE. 


PLATE  XIII. 

FiGr.  1.  Bacillus  filiformis  (Sternberg).  From  surface  of  agar  cnlture  ;  fuchsin  atain ; 
X  1,000. 

Fig.  2.  Bacillus  Martinez  (Sternberg).  From  single  colony  in  glycerine-agar  roll- 
tube;  fuclisin  stain;  X  1,000. 

Fig.  3.  Colonies  of  B.  filiformis  in  glycerine-agar  roll-tube;  end  of  5  days  at  35°  C. ; 
X  10. 

Fig.  4.  Colonies  of  B.  Martinez  in  gelatine  roll-tube  at  end  of  4  days  ;  X  10, 

Fig.  5.  Culture  of  B.  Martinez  in  flesh-peptone  gelatine;  end  of  4  days  at  22°  C. 

Fio.  6.  Culture  of  B.  filiformis  in  flesh-peptone  gelatine ;  end  of  7  days  at  22°  C. 


PLATE    XIII. 


Fig, 


Fig.   2, 


^i™ 


t» 


0 


Fig.  3. 


Fig. 


Fig.  5. 


Fig.  6. 


mELIOTYPE  printing  CO.    BOSTON, 


250  ETIOLOGY   A^^D   PKEVENTION    OF   YELLOW   FEVEE. 


PLA.TE  XIV. 

Fig.  1.  JBaeillus  I,  Havana,  1889.     From  gelatine  culture;  fachsin  stain;  X  1,000. 
Fig.  2.  Bacillus  E,  Havana,  1889.     From  gelatine  culture  :  fuchsin  stain  :   X  1,000. 
Fig.  3.  Bacillus  A,  Havana,  1889.     From  potato  culture;  fuchsin  stain ;   X  1,000. 
Fig.  4.  Bacillus  renalis  fortuitus  {^tGTnbevg.)     From  gelatine  culture;  fuchsin  stain ; 

X  1,000. 
Fig.  5.  Bacillus  U,  Havana,  1889.    From  single  gelatine  colony ;  fuchsin  stain ;  X 

1,000. 
Fig.  6.  Bacillus  Y,  Havana,  1889.     From  single  gelatine   colony;  fuchsin  stain;  x 

1,000. 
Fig.  7.  Single  colony  Bacillus  I.;  end  of  24  hours  at  20^0.  X  10. 
Fig.  8.  Bacillual,  culture  in  flesh-peptone  gelatine;  48  hours  at  room  temperature. 


PLATE    XIV. 


'     \-    "^-z    ,--  ■ 


Fig.   I 


rr:-? 


Fig.  3. 
^••.^  j^  ^  "Jii  •¥  ?v  ^*    ^ 


Fig.   7 


\Z.  * 


Fig.  8 


Fig.  5. 


Fig.  6. 


252    ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVEE. 


PLATE  XV. 

Fig.  1.  Bacillus  B,  Havana,  1889.  From  bottom  of  long  agar  "stick  culture;  "  fuch 
sin  stain;   X  1,000. 

Fig.  2.  ^aciZZusZ^,  Havana,  1889.    From  gelatine  cnlture ;  X  1,000. 

Fig.  3.  Bacillus  C,  Havana,  1889.     From  gelatine  cnlture ;   X  1,000. 

Fig.  4.  Bacillus  L,  Havana,  1889.     From  potato  culture,  4  days  old  ;   X  1,000. 

Fig.  5.  Bacillus  G-,  Havana,  1889.    From  single  gelatine  colony  ;  X  1,000. 

Fig.  6.  Slender  bacillus  from  specimen  of  Freire's  vaccine,  brought  from  Rio  de  Ja 
neiro  by  Dr.  Lane  in  a  sealed  glass  tube.  The  mount  was  made  immedi 
ately  after  opening  the  tube ;  stained  with  gentian  violet  j  X  1,000, 


PLATE    XV. 


Fig.   I 


^     ' - <  ^    I     •  r-   L 


Fig.  3. 


Fig.   2. 


.  -r 


Fig. 


Fig.  5, 


Fig.  6. 


HELIOTYPE  PRINTING  CO.    BOSTON, 


254     ETIOLOGY  AND  PREVENTION  OF  YELLOW  FEVEE. 


PLATE  XVI. 

Fig.  1.  Bacillus  gracilis  (Sternberg).    From  single  colony  in  gelatine  roll-tul)e;  x 

1,000. 
Fig.  2.   Bacillus  coli  similis  (Sternberg).    From  single  colony  in  gelatine  roll-tube; 

X  1,000. 
Fig.  3.  Bacillus  gracilis.  Colonies  in  gelatine  roll-tube  at  end  of  24  hours  at  22°  C. ; 

X  10. 
Fig.  4.  Bacilhis  coli  similis.    Colonies  in  gelatine  roll-tube  at  end  of  24  hours  at  22° 

C.  ;  X  12. 
Fig.  5.  Bacillus  gracilis.    Colonies  in  gelatine  roll-tubes  at  end  of  48  hours  at  22°  C. ; 

X  12. 
Fig.  6.  Bacillus  coli  similis.     Culture  in  flesh-peptone-gelatine  at  end  of  7  days  at 

20  C. 
Fig.  7.  Bacillus  coli  similis.    Colonies  in  gelatine  roll-tube  at  end  of  five  days  at  20° 

C.J  Xl3. 


PLATE    XVI. 


.  r-^- 


••^i^^ 

^^-^X"^" 


Fig. 


•      «. 


*  ..♦ 


>     • 


^    f 


Fig.  3. 


Fig. 


Fig.  5, 


Fig.  6. 


Fig.  7. 


EllOTVi>E  PRINTING  CO.    BOSTON 


256     ETIOLOGY  AND  PEEVENTION  OF  YELLOW  FEVEK. 


PLATE  XVn. 

Fig.  1.  Streptococcus  cadaveris  (BteraheTg)  (Streptococcns  pyogenes?).  From  culture 

in  agua  coco  ;   X  1,000, 
Fig.  2.  Streptococcus  Havaniensis.    From  vomit  (not  black)  kept  in  collecting  tube  for 

24  hours.     Yellow- fever    case  in   military  hospital,   Havana,   1889;  X 

1,000, 
Fig.  3.  Micrococcus  luteus.    From  gelatine  culture ;  X  1,000. 
Fig.  4.  StrejitococcusliqtiefaciensifiteTiiheTg).    From  anaerobic  culture  in  flesh-peptone 

gelatine;   X  1,000, 
Fig.  5.  Colony  in  gelatine  roll-tube  of  Streptococcus  Uquefaciens  ;  X  10. 
Fig.  6.  Streptococcus  cadaveris.     Colonies  in  gelatine  roll-tube  ;   XlO. 
Fig.  7.  Streptococcus  Uquefaciens,    Culture  in  flesh-peptone-gelatine;  end  of  7  days 

at22oc. 


PLATE    XVII. 


!^ 


Fig.   I . 


••^     v 


v» 


Fig.  3 


••I* 


^"^7^ 


I 


j'f  .v.. 


18L 


<•     ^ 


Fig.   2. 


>\ 


i  «  ^^       - 


Fig.  4. 


m 


Fig.  5, 


Fig.  7. 


Fig.  6. 


YPE  PRINTING  CO.,   BOSTON 


258  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


PLATE  XVIIL 

Fig.  1.  Torula  gastricns  (Sternberg).    From  surface  of  agar  culture.   Not  stained; 

X  about  400. 
Fig.  2.  Micrococcus  hepatious  (Sternberg).    From  surface  of  agar  culture.    Bismarck 

brown  stain  ;   X  825. 
Fig.  3.  Micrococcus  J.   (Havana,   1888);   X    1,000.     Obtained   from   liver  of   case  8, 

kept  48  hours  in  an  antiseptic  wrapping. 
Fig.  4.  Micrococcus  FinJayensis  {Bternherg).    From  surface  of  agar  culture.    Bismarck 

brown  stain  ;  X  825. 
Fig.  5.  Micrococc^is  versatilis  albusiSternheTg).  From  a  culture  m  agua  coco.    Fuchsin 

stain  ;   x  1,000. 


PLATE    XVIII. 


•k  •  •  » 


nv^ 


*M 


.*?•* 


>.. 


..*•«'*- 

•^ 

•;<. 


•.-*.* 


Fig.   I. 


Fig.   2. 


Fig.  3. 


1^: 


260  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


*  PLATE  XIX. 

I-'iG.  L   BncUhis  Ravanievsis  (Sternberg).     Potato  culture  at  end  of  15  days  at  room 

temperature. 
Fig.  5!.   BacVliis  pyocyanns.     Agar  culture  at  end  of  &  days  at  room  temperature. 
Fig.  o.  Bacillus  pyocyan us.     Potato  culture  at  end  of  5  days. 


n^ATE  xrs: 


t^ 


Fi6  1 


A.HaEnXCn.LitliDcaustiE^aHininrE. 


262  ETIOLOGY    AND    PREVEKTION    OF    YELLOW    P^EVEJR. 


PLATE  XX. 

Fig.  1.  Micrococcus  tetragenus  versatilis  (Sternberg).    Agar  culture  at  end  of  10  days, 

at  2-20  C. 
Fig.  2.  Micrococcus  of  Freire.     Agar  culture  at  end  of  7  days,  at  22^  C. 
Fig.  3.  Bacillus  of  Gibier.     Agar  culture  at  end  of  12  days,  at  22^  C. 


P'X.ATE  XS 


J'ici  3 


A.Hdeh  XCo.LirtiQcausticBahimore. 


264  ETIOLOGY    AND    PREVENTION    OF    YELLOW    FEVER. 


PLATE  XXI. 

Fig.  1.  Bacillus  fluorescevs  liquefadens.     Potato  culture  at  end  of  1  montli  at  room 

temperature. 
Fig.  2.  Bacillus  fluorescens  liquefaciens.     Gelatine  culture  at  end  of  1  month  at  room 

temperature. 
Fig.  3.  Bacillus  liquefaciens  commune  (Sternberg,)     Potato  culture  at  end  of  20  days 

at  room  temperature. 


P»LATE  XXL 


A.HnEniCc.LithQcaustic.BalliniDrE. 


INDEX 


Page. 

Abbott,  Dr.  A.  C 203 

Accliniatizatiou 53 

Acknowledo;ment8 9 

Aerobic  cultures  in  flesh-peptone-gelatine,  etc 104 

Aerobic  cultures 113 

from  stomach  and  intestine 11.5 

Agar-agar  jelly,  aerobic  cultures  in,  etc 104 

Age 51 

(tables) 52 

Alcohol,  examination  of  tissues  preserved  in 109, 136 

Anaerobic  cultures 105, 107, 119 

Animals,  experiments  upon 108 

in  tabular  form 170, 172 

results  of 123 

Antiseptic  wrapping,  result  of  examination  of  tissues  kept  in lil 

virulence  of  liver  tissue  when  kept  for  4^i  hours  in 127 

Babes,  Dr 175 

bacillus  of,  in  kidney,  photo-illustration  of 179 

Babes  and  Lacerda,  the  bacillus  of 174 

Bacilli,  straight,  in  glomerulus  of  kidney,  photograph  of 139 

liquefying,  notes  with  reference  to  the  presence  of 168 

Bacilli lei 

Bacillus  of  Dr.  Paul  Gibier 167 

Lacerda  and  Babes 174 

Babes  in  kidney,  photo-illustration 179 

X,  characters  of,  (Nos.  lto35) -. L-^9-218 

No.  1 :   Bacterium  coli  commune,  characters  of  (Escherich)  (Stern- 
berg)    181 

X,  No.  2  (Havana,  1889) 187 

X,  pathogenic  for  rabbits  when  injected  into  cavity  of  abdomen 192 

subcutaneons  injections  into  rabbits 192 

acidiformans,  No.  3  (Sternberg) 200 

cavicida  Havaniensis,  No.  4  (Sternberg) 202 

hepaticus  fortuitus.  No.  5  (Sternberg) 2u5 

intestinus  motilis.  No.  6  (Sternberg) 205 

cavia  fortuitus,  No.  7  (Sternberg) 206 

caniculacida  Koch  (No.  8) 206 

Havaniensis,  No.  9  (Sternberg) .  207 

vacuolosis.  No.  10  (Sternbei  g) 208 

fluorescens  liquefaciens.  No.  11  (Sternberg) 208 

pyocyanus.  No.  12  (Gessard) 209 

liquefaciens  commune,  No.  13  (Sternberg) 209 

subtilis,  No.  14  (Ehrenberg) 210 

subtilis  similis.  No.  15  (Sternberg) 210 

intestinus  liquefaciens,  No.  16  (Sternberg) 211 

265 


266  INDEX. 

Page. 

Bacillus  filiformis,  No.  17  (Sternberg) 211 

cadaveris,  No.  Id  (Sternberg) "212 

cadaveris  grandis,  No.  19  (Sternberg) 213 

Clostridium  cadaveris,  No.  20  (Sternberg) 213 

anaerobicus  liquefaciene,  No.  21  (Sternberg) 214 

renalis  fortuitus,  No.  22  (Sternberg) 214 

Martinez,  No.  23  (Sternberg) 214 

lutens  couimnne,  No.  24  (Sternberg) 215 

L,  Havana,  1889  (No.  25) 215 

C,  HavaTia,  1889  CNo.  26) 215 

K,  Havana,  1889  (No.  27) 215 

llavaniensis  liquefaciens  (No.  28) 215 

A,  Havana,  1889  (No   29) 216 

E,  Havana,  1889  (No.  30) 216 

U,  Havana,  1889  (No.  31) 216 

Y,  Havana,  1889  (No.  32) 216 

gracilis,  Sternberg  (No.  33) 216 

coli  similis,  Sternberg  (No.  34) 218 

B,  Havana,  1889,  Sternberg  (No.  35) 218 

Bahama  Islands,  yellow  fever  in 42 

Bicarbonate  of  sodium  and  bichloride  of  mercury  in  treatment  of  yellow  fever.  87-96 

formula 88 

Billings,  Dr.  Frank 176 

"Black  vomit,  "  collected  during  life  and  injected  at  once  into  guinea-pigs  is 

not  pathogenic 131 

Blood  and  liver  tissue  from  a  recent  autopsy  not  pathogenic  for  guinea-pigs  or 

rabbits 125 

Booker,  Dr 184 

Brazil  and  Mexico,  summary  of  investigations  in 16-35 

Buckley,  Dr.  W.  C 88 

Burgess,  Dr.  D.  M 9,84,137,176 

letters  of 8-5-87,138 

reports  25  cases,  recovered 94 

Cabera,  Dr.  Francis 85 

Carmona,  Dr.  y  Valle,  yellow  fever  "germ  "of 163 

Charleston,  S.  C,  mortality  from  yellow  fever  in  (table) 44 

Chattanooga,  Tenu.,  epidemic  at  (1878) 61 

Cleary,  Dr.  R 90 

Cleveland,  Grover,  President  of  the  United  States,  letter  of 11 

Causes,  predisposing  (constipation,  plethora,  fatigue,  dibility,  exposure,  grief 

or  fear) 56 

Clinical  history 65-72 

Cochran,  Dr.  Jerome 9, 88 

Comparative  experiments 129 

Conclusions 221-223 

Conyngton,  Dr.  E.  J 9,88 

Councilman,  Dr,  "William  T 10 

report  upon  material > 140 

pathological  histology  of  yellow  fever.  151-153 

Cross,  Dr.  B.  F 9,88 

"Cryptococcus  Xanthogenicus,"  Dr.  D.  Freiru's 160 

Cultures,  aeorbic 104 

ftom  stomach  and  intestine 115 

anaeorbic 105-107 

sterilized  by  heat,  experiments  with 195 


INDEX.  267 

Page 

Decatur,  Ala.,  results  of  treatment  in 88 

Dejecta  of  yellow-feYer  patients  should  be  regarded  as  infections  material 223 

Delgado,  Dr.  Claudio 9,  HiG 

Detmers,  Dr 179 

Diagnosis - 74-78 

Drum,  R.  C,  Adjutant-General 7,8 

Dogs,  experiments  on 194 

Duran,Dr 93 

Eudicott,  William  C,  Secretary  of  War,  orders  of 7,8 

Etiology 49 

of  epidemics 57 

Experiments 192,194,202,204,209,210 

comparative 129 

in  Havana,  in  ld89 128-130 

upon  animals 108 

rabbits 129 

with  cultures  sterilized  by  heat 195 

Faria,  Dr.  Eocha 91 

Fatty  degeneration  of  ]i%^er,  photograph  of 156 

Fernandos,  Dr.  Santos ^ 9 

Finlay ,  Dr.  Carlos 9 

yellow-fever  germ  of 164 

Formula  of  Dr.  Sollace  Mitchell 93 

Dr.  Martinez „. 95 

orginal ;  increased  doses  of  two  ingredients 94 

Freezing  does  not  destroy  viruleuce 199 

Freire,  Dr 33-35,  124,  125 

relative  to  inoculations  by  (See  Annual  Report  of   Marine  Hos- 
pital Service,  1889) 28 

Freire's  "  Cryptococcus  Xanthogenicus" 160 

Galveston,  Tex.,  mortality  from  yellow  fever  in  (table) 44 

General  results  of  investigations  made 112 

"Germ,"  yellow-fever,  of  Dr.  Carmona  y  Valle 1G3 

Dr.  Carlos  Finlay 164 

Gibier,  Dr.  Paul 91,  92,  116,  117,  167 

result  of  researches  by 31 

results  obtained  contradict  Dr.  Freire 167 

the  bacillus  of 167 

Goes,  Dr.  Araujo 161,  175 

Guardia,  de  la  Vincent 91,  92,  94 

Guinea-pigs  "black  vomit"  collected  during  life  and  injected  into,  is  not  path- 
ogenic         131 

and  rabbits,  material  from  the  intestine  not  always  fatal 134 

experiments  on 194 

experiments  on,  in  tabular  form 171 

material  from  stomach,  soon  after  death,  virulent  for 130 

material  oljtained  from  small  intestine  soon  after  death,  when  in- 
jected, virulent  for 131 

Hamilton,  John  B.,  Supervising  Surgeon-General  Marine  Hospital  Service,  let- 
ter to  Secretary  Windom 3 

thanks  to , 10 

Havana,  Governor-General  of,  thanks  to 9 

investigations  made  in,  in  1888-'89 97 

"  monthly"  maximum  and  minimum  deaths  by  yellow  fever, (1870-'79).        39 


268  INDEX. 

Page. 
Havana,  mortality  from  yellow  fever,  1870-79  (Chaill^'s  report  to  national  board 

of  health) 60 

notes  of  experiments  in,  in  1889 128-130 

total  deaths  by  yellow   fever   lb70-'79  (from  preliminary  report   of 

yellow  fever  commission) 39 

Hepatitis,  acute,  with  necrosis  of  liver  cells,  photograph  of 150 

photograph  of 154, 155 

Hoagland,  Dr.  C.  N 9 

Injections  into  the  intestine 174 

Illustrations,  photo 139,  149-151,154-159,179,213 

Immunity 53 

Incubation 65 

Infection,  mode  of 56 

Intestine,  injections  into  the.' 174 

material  from,  not  always  fatal  to  guinea-pigs  and  rabbits 134 

small,  material  from,  injected  soon  after  death,  virulent 131 

and  liver,  material  from,  kept  in   collecting  bulb  for  2  weeks  loses 

virulence 134 

Introduction 11-35 

Jacksonville,  Fla.,  results  of  treatment  in 89 

Johns  Hopkins  Universitj^,  acknowledgment  to  president  and  trustees  of  the..  9 

investigations  made  in 97 

Kemp,  Dr.  George 163 

Kidney,  acute  parenchymatous  nephritis  (photograph) 151 

straight  bacilli  in  glomerulus  (photograph) 139 

Kinyoun,  J.  J.,  assistant  surgeon  Marine  Hospital  Service 33 

Koch's  laboratory,  visit  to 137 

Lacerda  and  Babes,  the  bacillus  of 174 

Liquefying  bacilli,  notes  with  reference  to  the  presence  of. 168 

Littlejohn,  Dr.  E.  M 9,8^,101 

Liver  cells,  fatty  infiltration  of,  photograph  of 149 

necrosis  of,  hepatitis,  acute,  photograph  of 150 

necrotic,  photograph    of 157 

fatty  degeneration  of,  photograph  of 156 

hyaline  degeneration  of,  photograph  of 158 

section  of,  photograph  of 154,  '  55 

tubules  containing  colloid  material,  photograph  of 159 

and  intestine,  material  from,  kept  in   collecting   bulb   for  2  weeks  loses 

virulence 134 

xMall,  Dr.  F.  P 10 

Marine  Hospital  Service,  report  of  Dr.  Sternberg  in  annual  volume  for  1889 12 

Martin,  Dr.  N.  H 9 

Martinez,  Dr.  Emilio 9,94,95,140,  176 

Macfeely,  R.,  Acting  Secretary  of  War 7 

Malo,  Dr.  Fernandes 9 

Material 97-101 

method  of  collecting 102 

from  stomach  so(^n  after  death  is  virulent  for  guinea  pigs     130 

intestine  not  always  fatal  to  guinea-pigs  and  rabbits 134 

liver  and  intestine,  kept  in  collecting   bulb  2  weeks  loses  viru- 
lence         134 

small  intestine  when  injected  soon  after  death  virulent 131 

Mercedes  Hospital  statistics  (1882  to  1888) 95 

Methods  of  research 104-111 

Mexico  and  Brazil,  summary  of  investigations  in 16-35 


INDEX.  269 

Page. 

Micrococci  not  found  in  blood  and  tissues  of  yellow-fever  cadavers 163 

Micrococci 218 

Micrococci,  No.  1.  Staphylococcus  pyogenes  aureus 218 

No.  2.  Streptococcus  cadaveris  (Sternberg) 218 

No.  3.  Streptococcus  havaniensis  (Sternberg) 219 

No.  4.  Streptococcus  liquefaciens  ('Sternberg,  Escbericb) 219 

No.  5.  Micrococcus  hepaticus  (Sternberg) 219 

No.  6.  Micrococcus  Finlayensis  (Sternberg) 219 

No.  7.  Micrococcus  versatilis  albus 220 

No.  8.  Micrococcus  luteus 220 

Torula  gastricus  (Sternberg) 220 

Micrographs,  photographic  reproductions  of  photo 139, 149-151, 154-159 

Microorganisms,  description  of,  which  have  been  claimed  to  be  the  cause  of 

yellow  fever 160 

direct  examination  of  "  smear  preparations"  from  blood  and 

tissues,  for 104 

isolated  from  yellow-fever  cadavers,  description  of 181 

photomicrographs  of,  encountered 109 

Mitchell,  Dr.  Sollace 89 

formula  of 93 

Mobile,  Ala.,  mortality  from  yellow  fever  in  (table) 44 

Montgomery,  A.la.,  paper  read  at  quarantine  conference 13-16 

Mortality 73 

Necrotic  liver  cells,  photographs  of 1.57 

Nephritis,  acute  parenchymatous,  photograph  of 151 

New  Orleans,  La.,  mortality  from  yellow  fever  in  (table) 44 

Nunez,  Dr.  Emiliano 9 

Orders 7 

Pardinas,  Dr.  Antonio 9 

Patliological  auatomy  and  histology 146 

Peusacola,  Fla.,  mortality  from  yellow  fever  in  (table) 44 

Philadelphia,  yellow  fever  in 45-47 

Photomicrographs  of  microorganisms  encountered 109 

Photo-illustrations 139, 149-151, 154-159, 179,213 

Plates  I  to  XXI 224-264 

[See  Bacillus,  p.  181-218,  and  Micrococci,  p.  218-220.] 
Predisposing  causes  (plethora,  coustipation,  fatigue,  debility,  exposure,  grief 

or  fear) 56 

Proguosis , 72 

Prophylaxis 63 

Quarautine  conference  at  Montgomery,  Ala.,  paper  read  at 13-16 

Range,  Dr  . . , 125 

Rabbits,  experiments  upon 129, 192 

in  tabular  form 170 

and  guinea-pigs,  material  from  the  intestine  not  always  fatal 134 

Race,  immunity  of  colored 50 

Reeves,  Dr.  James  E 9, 140, 176 

"  Reference  Handbook  of  the  Medical  Sciences,"  article  on  yellow  fever  repro- 
duced   36-84 

Report :  Investigations  made  in  Havana,  1888  and  1889,  Decatur,  Ala.,  1888,  and 

in  the  laboratories  of  the  Johns  Hopkins  University 97 

Results,  general 112 

of  examination  of  tissues  kept  in  antiseptic  wrapping 121 

experiments  upon  animals 123 


270  INDEX. 

Page. 

Rio  de  Janeiro,  mortality  from  yellow  fever  (1850  to  1886) 41 

1886  (table) 60 

1851  to  1870  (table) 60 

results  of  treatment  at -• ^0 

Seitz,  Dr.  Carl 137,178 

Sex 51 

Shreveport,  La.,  mortality  (1873) 5^ 

Slicle8,li8tof  (180) 141-144 

"  Smear  preparations,"  direct  examination  of,  from  the  blood  and  tissues,  for 

microorganisms 104 

examination  of 112 

"Smear  preparations" 145 

Smith,  Dr.  Henry 52 

Stomach,  material  from,  soon  after  death,  viriileut  for  guinea-pigs 130 

Surgeon-General  J.  B.  Hamilton,  thanks  to 10 

Susceptibility 50 

Table — Deaths  classified  by  age,  New  Orleans 52 

among  childreu  born  in  New  Orleans 52 

Epidemic  at  Chattanooga,  Teun 61 

Experiments  on  animals 170-172 

Monthly  maximum  and  minimum  deaths  by  yellow  fever  lu  Havaua, 

1870-'79 ----         39 

Mortality  from  yellow  fever  in  Vera  Cruz  (July,  1867,  to  December, 

1881) 40 

Mortality  from  yellow  fever  in  Rio  de  Janeiro  (1830  to  1886) 41 

Mortality  from  yellow  fever  in   Charleston,   Pensacola,  Mobile,   New 

Orleans,  Galveston 44 

Mortality  per  thousand  among  different  races 51 

Mortality  from  yellow  fever  in  Rio  de  Janeiro  (1883) 60 

(January,   1851,  to  July, 

1870) 60 

Mortality  fro-n  yellow  fever  in  Havana,  1870  to  1879 60 

Mortality  at  Vera  Cruz  for  4  years,  1878  to  1881 61 

Statistics  of  yello  sv  fever  in  Mercedes  Hospital  ( 1832-1883)  95 

Total  deaths  by  yellow  fever  in  Havana,  1870-79 39 

Temperature  charts 67 

Therapeutic  Gazette,  new  method  of  treatment  published  in 85-87 

article,  May  15,  1889 87-96 

Tissue,  blood  and  liver,  from  a  recent  autopsy,  not  pathogenic  for  guinea-pigs 

or  rabbits - 1-5 

examination  of,  kept  in  antiseptic  wrapping 107 

preserved  in  alcohol 109, 136 

kept  in  antiseptic  wrapping,  result  of  examination  of 121 

liver,  virulence  of,  kept  for  48  hours  in  antiseptic  wrapping 127 

Tomayo,  Dr.  D.,  result  of  researches  by 32 

Treatment 78-87 

bicarbonate  of  sodium  and  bichloride  of  mercury 87-96 

formula 88 

United  States,  yellow  fever  in  the 43-49 

(table) 44 

by  States 45,47,48,49 

Urine,  yellow-fever,  not  nathogenic  for  rabbits 127 

Vandeman,  Dr.  J.  H 61 

Vera  Cruz,  mortality  from  yellow  fever  July,  1867,  to  December,  1-81 40 

mortality  for  four  years,  1878  to  1881 61 


INDEX.  271 

Page. 

Vildosola,  Dr.  Francis  I 9 

Virulence  of  liver  tissue  kept  for  48  hours  in  an  antiseptic  wrapping 127 

Wakefield,  Dr.  A.  J 89,90 

Welch,  Dr.  Wm.  H 9 

Welch's  laboratory 203 

Weiss,  Dr.  Raphael 85 

White  rats,  experiments  on,  in  tabular  form 172 

Windoni,  William,  Secretary  of  Treasury,  letter  of  Dr.  Hamilton  to 3 

Wood's  "Reference  Handbook  of  the  Medical  Sciences,"  article  on  yellow  fever 

reproduced 36-84 

"Wood's  Handbook  of  the  Medical  Sciences,"  portion  of  article  relating  to 

pathology  of  yellow  fever 146-151 

Yellow  fever,   "  monthly  "maximum  and  minimum  deaths  from,  in  Havana, 

1870-'79 39 

total  deaths  from,  in  Havana,  1870-79 39,  60 

mortality  from,  in  Vera  Cruz,  1867  to  1881 ■ 40 

1878  to  1881 60 

Kio  de  Janeiro,  1850  to  1886 41 

1886  (table) 60 

1851  to  1870  (table) 60 

results  of  treatment  at 90 

in  the  United  States 43-49 

(table) 44 

by  States 45,47,48,49' 

Charleston,  Galveston,  Mobile,  New  Orleans,  Pensacola 44 

Chattanooga,  epidemic 61 

Decatur,  Ala.,  results  of  treatment  in 88 

Philadelphia 45-47 

Shreveport •. o2 

cadavers,  micrococci  not  found  in  blood  and  tissues  of 163 

description  of  microorganisms  isolated  from 181 

"germ"  of  Dr.  Carmona  y  Valle 163 

Carlos  Finlay 161 

notes  of  experiments  made  in  Havana  (1889) 128-130 

predisposing  causes 56 

urine  not  pathogenic  for  rabbits 127 


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Annex 


